Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Rochester Institute of Technology RIT Scholar Works Theses Thesis/Dissertation Collections 5-1-1992 Spectral analysis of heart rate variability: Acquisitionalysis software development David James DeLong Follow this and additional works at: http://scholarworks.rit.edu/theses Recommended Citation DeLong, David James, "Spectral analysis of heart rate variability: Acquisitionalysis software development" (1992). Thesis. Rochester Institute of Technology. Accessed from This Thesis is brought to you for free and open access by the Thesis/Dissertation Collections at RIT Scholar Works. It has been accepted for inclusion in Theses by an authorized administrator of RIT Scholar Works. For more information, please contact [email protected]. Spectral Analysis of Heart Rate Variability: Acquisition/Analysis Software Development by David James DeLong A Thesis Submitted in Partial Fulfillment of the Requirements for the Degree of MASTERS OF SCIENCE in Mechanical Engineering Approved by: Mark H. Kempski, Ph.D. (Thesis Advisor) Rochester Institute of Technology Brahm Goldstein, M.D. (Medical Advisor) University of Rochester Medical Center Edward R. Salem, Ph.D. Rochester Institute of Technology Joseph S. Torok, Ph.D. Rochester Institute of Technology Charles W. Haines, Ph.D. (Department Head) Rochester Institute of Technology Department of Mechanical Engineering College of Engineering Rochester Institute of Technology Rochester, New York 14623 May 1992 Title of Thesis Spectral Analysis of Heart Rate Variability: Acquisition/Analysis Software Development I, David James DeLong, grant permission to the Wallace Memorial Library to reproduce my thesis in whole or in part. Any reproduction will not be for commercial use or profit. The author makes no claims as to the reliability of the methods, procedures, or results within the enclosed report for the purposes of medical diagnosis, treatment, or prognosis of any human or other living organism. Date Abstract This the work develops the heart spectral content of diographic (EKG) the within into variability The location waveform. head trauma spectral content of els of serum the heart rate variability frequency activity and strength of the study have variability the Current investigations subject. revealed specific as both trauma severity frequency body fact, interest in the band (0.01-0.15 temperature adult) of parasympathetic a prominent peak represents Clinical has shown heart Hz) application of that proved chances elevated and Acute and spectral power power spectral the high systemic arterial The levels have blood a characteristic at of critical care neurophysiology. respiratory at severe shown frequency band indicator medicine, nervous system as well frequency band sinus arrhythmia) a normal is only. human the respiratory frequency. techniques described herein of im brain injury. In contrast, brain-dead pe found to little power are possess near-zero that decreases in pressure with density regulation) approximately 0.20 Hz (of low-frequency HRV change low-frequency low-frequency in indicative HRV high-frequency power. power and HRV power, of endotoxin-induced septic shock. acquisition/analysis package beneficial to as pressure The high acquisition and analysis patients were animal studies may be the blood system activity. variability for recovery from diatric head trauma and arterial activity (such located rate are also signal. some parasympathetic nervous indicative In as The lev norepinephrine, (0.15-0.50 Hz). The low frequency band is indicative of sympathetic activity (such between correlations and overall patient recovery. epinephrine and regions are of particular waveform, the low an electrocar sympathetic and parasympathetic a possible correlation with rate derived from content catecholamines, specifically investigated for the heart patients signal to investigate frequency autonomic nervous system of pediatric Two rate information concerning reveals general of an acquisition/analysis software application described in this and advance our work may, understanding therefore, prove of cardiovascular Acknowledgements The task tribulations completing this during appreciation the of would University academic career. would of and like to machine are like to challenging extend my experience of all thanks greatest guidance and monumental patience of and during the Pediatric Critical Care Center in the Rochester Medical Center for allowing head trauma extend greatly my neering Department for his theory would like to thank Dr. Brahm Goldstein the human I I most this thesis. research work on pediatric of has been the to Dr. Mark H. Kempksi for his completion of I my work its applications, His the opportunity to efforts assist in his towards my understanding appreciated. sincere efforts patients. me thanks to Dr. Edward Salem towards my understanding without which this of work could not of the Electrical Engi digital be signal processing accomplished. Contents Abstract i Acknowledgements ii Table v of Contents List of Figures List of Tables 1 ix Introduction 1.1 1.2 2 viii 1 Mechanics the Cardiovascular System of 1 1.1.1 Physical Components in the Cardiovascular 1.1.2 Cardiovascular Function 1.1.3 Timing 1.1.4 Regulation Mechanisms Psuedo- Periodic 1.2.2 Psuedo- Periodic of Variability Background of Heart Rate 1.4 Justification of Research Humans 1.4.2 Potential of Cardiovascular in Physiological Waveforms Cardiovascular Variations 1.3 of Cardiologic Events Variations in Physiological Waveforms Origins Use 3 Feedback Mechanisms and 1.2.1 1.4.1 of 4 Activity . 9 16 17 18 19 Variability 23 and use as a 1 system 23 Rabbits Diagnostic and Prognostic Tool 24 25 Methodology 2.1 Methods Employed in Previous Experimental Work 25 2.2 Preparation Subjects 27 2.3 Collection Physiologic Data 29 2.4 Analysis of of of Study 30 Physiologic Data in 3 4 Detection 2.4.2 Creation 2.4.3 Power Spectral Analysis 2.4.4 Respiratory Frequency Verification 44 2.4.5 Statistical Analysis 44 of of QRS-Complexes the HRV Signal from R-wave Peak Location Data of the HRV Dataset Results 31 . . 39 42 46 3.1 Pediatric Brain 3.2 New Zealand White Rabbits 47 3.3 Software Application 47 Injury Patients 46 Discussion 4.1 4.2 5 2.4.1 55 Acquisition/Analysis Software Development 4.1.1 Hardware Requirements 55 4.1.2 QRS Complex Detection 57 4.1.3 Respiration Signal Analysis 60 4.1.4 Application Features 64 4.1.5 Software Limitations &: Operational Notes 65 Clinical Conclusion and and Result Interpretation Laboratory Appendix A A. 2 - Signal 71 Processing Continuous-Time Analog A. 1.1 The Fourier Series A. 1.2 Spectral Content Fundamentals of 76 76 Signals 76 Analog Signals 78 83 Discrete Signals A. 2.1 66 60 Recommendations References & Citations A.l 55 Discrete Fourier Transform IV 84 A. 2. 2 A. 3 A. 4 Spectral Content Considerations of the of Spectral Abberations A. 3. 2 Reducing Appendix B Appendix C Appendix D Appendix E - - - - 89 Discretization Process A. 3.1 Power Spectral 88 Discrete Signals 90 Spectral Abberations 92 Density Determination 94 Rabbit Endotoxin Study 95 Grant Proposal 101 Related Published Abstracts Sample Program Output for Software Design and a Program Normal Analysis Operating Manual 107 115 List of Figures 1 The human heart in functional 2 Schematic 3 A typical lead II EKG marking distinctive 4 An 5 actual representation of EKG the EKG superimposed on the event series tion A Comparison from the EKG 7 Example 8 A QRS representing R of 9 during that cardiac the 5 A QRS relative waveform stage complex Example activity is respiration activity (the pulse) is 9 peaks in the EKG (a). R-R interval dura by a obtained via interpolation 1987) sizes 26 of to the 'blocks' used 33 zoom-window stage EKG tracing an scan- the data processing window edge. and point R 35 Point L marks a left window marks a right window edge slice 37 detected the near of computer processed A 'left' to include 95 adjustment glitches at points Example and B of computer processed edge of points the first is necessary instantaneous heart the are rate result of glitches IHR dataset scan-window. 37 (IHR) dataset. in the EKG after application of signal. 40 Changes in jured power spectral patient with cerebellar 40 the IHR. Patch algorithm 12 8 cardiac cycle. the R-S interval The 11 the the Q-R interval Zoom-window 10 of complex sliced edge slice of points the heart respiration signal large T-waves in of system of tachogram (b). Interval function series or 2 tracing. Note that signal and (c). (Reproduced from Baselli 6 form the conduction and respiration superimposed on An schematic GCS=3 herniation magnitude of and the Y-axis density (top) of and HRV in the a four-month same patient brain death (bottom). old brain in 24 hours later after Note lOx difference in 50 scales vi 13 Temporal brain death. Temporal of interfered 15 An in changes brain death. with the EKG example rate power approaches zero plasma catecholamine almost waveform levels in 2/3 non-detectable catecholamine of in 3/3 51 (pg/ml) during norepinephrine The third the development during brain death and brain death. Plasma levels become opment total heart tonsillar herniation velopment of (E) rate power spectra Low-frequency patients with 14 in heart changes patient was (NE) patients the de and epinephrine with the devel receiving dopamine that 52 assay illustrating anomalous occurrences in the sec 58 ond panel 16 An anomalous point at cs 34 seconds in an example EKG tracing 59 17 An anomalous point at ss 40 seconds in an example EKG tracing 60 18 Extraction from {IHR. in EKG example FIR digital filter Plot A-l Example of A-2 Example of summed A-3 The A-4 The two-sided three Note that Representation A-6 The periodic A- 7 The by (composite) of a is of index 63 79 signals 79 signal spectrum discretely nature analog spectrum of frequency the DFT effect frequency the The example function composite analog record . waveform. is an odd function. . resulting from the assumptions 87 of a non-integer number of cycles in a 90 sinusoid signal A-8 Leakage effects in the 'windowing' effect of 81 83 signal algorithm in the time domain 80 with amplitudes one-half phase spectra sampled the time example composite waveform. the of an even one-sided spectrum. A-5 made mono- amplitude spectra those for the points 61 coefficients versus coefficient frequency one-sided illustrating effects anomalous waveform 19 of dataset Values} frequency domain to minimize it vn of a mono-frequency sinusoid and 91 A-9 The effect of windowing in the time domain vni 93 List 1 of Tables Age, sex, Glascow Coma Score, basal cardiorespiratory parameters, heart power spectral values and plasma catecholamine 2 Cardiorespiratory, after cold pressor 3 Changes in power spectral and catecholamine testing. Data in the New Zealand White 4 Hardware 5 Disk file expressed as mean various physiologic parameters used rabbit, for development storage requirements (mean S.E.M). levels (mean changes before and 49 S.E.M resulting from endotoxin shock 53 S.E.M.) 55 versus actual application use for D/A integer data for nominal 256 subfile 56 recording A-l Comparison 48 of the Number of Real Multiplications for the DFT IX and FFT. 88 1 INTRODUCTION 1 Introduction 1 Short-term ships in variations cardiovascular between the circulatory, neural, of an abnormal physiologic The human The The focus affected. the is following responsible sections for the distribution is to brief present a Physical Components in the Cardiovascular The cardiovascular system sels. The heart functions form the distribution of consists network systemic is composed of as a positive network be during on head of blood in the body. overview of the normal through the heart and a complex network of displacement 'cardiac which blood of blood to the lungs and pump'. moves about the body, and blood The blood the body. The veins, in ves vessels vascular order of through the pulmonary flow and circulations, respectively, is depicted schematically in Figure 1. The pulmonary circulation delivers deoxygenated blood to the lungs for circulation provides To provide oxygen pump and timing properties which are modulated pulmonic and action of nutritional and by which the heart is must support external neural networks largely reoxygenation. for tissue control, the heart systemic vascular flow. Vascular impedance, pumping system arteries, arterioles, capillaries, venules, from the heart. The flow The these bi present work will and abnormal control activity, event cardiovascular system. 1.1.1 mands. In the and regulation of the of the body. the Cardiovascular System of cardiovascular system main purpose of human by functional inter-relation and sepsis conditions. Mechanics 1.1 interaction normal cardiovascular control via autonomic neural trauma determined are and endocrine systems of condition, the may be adversely systems ological activity systemic metabolic de possesses spontaneous contractile impulses. impart vascular resistive, is the overcome. and organ The The impedance to blood afterload against magnitude of the which the is dy- afterload 1 INTRODUCTION lining nside of heart (ndocardium) RIGHT HEART receives tEFT HEART blood from the receives body and pumps it to artery where if the picks up oxygen-full blood from the lungs through the pulmonary and lungs pumps it through the aorta to the body. fresh oxygen. bag TRUNK & LEGS Figure 1: The human heart in functional Heart Association, Inc.) schematic of tissue surrounding heart (pericardium) form. (Courtesy of the American INTRODUCTION 1 adjusted namically 3 primarily by the for arteriole's smooth muscle accounts tered tissue oxygen and nutrient the smooth muscle of adjustments of blood demand. Adjustments in The arterioles. tone1 the of in response to afterload will therefore affect delivery al cardiac output and performance. Neurologic, be obtained physiologic, endocrine, from physiology texts. human physiology within this are covered tissue, 1). The right tricuspid valve, the points of cursory interest concerning below to facilitate understanding the mitral valve. pulmonic consists the left heart The pulmonary the and value, The heart is material of the anatomically right consists of the left vasculature systemic atrium vasculature is discussed and fibrous consists of functionally and by the by supplied connec two distinct interfaced ventricle atrium and ventricle supplied is comprised of The heart and a neural network. chambers which are heart, and Function. and tissue, cardiac muscle two interconnected ure some function may work. General Heart Structure of However, of cardiac Cardiovascular Function 1.1.2 tive details and pharmacologic pairs (Fig by the interfaced by right ventricle via the the left ventricle via the aortic valve. The contraction of the monary artery (from the body locations. The compliance and This 'hydraulic 'Tone is and ventricle can into the be felt filter' dampens the is attenuated capillary nearly steady overall Higher impulse frequencies (non-pulsatile) [7, by The vascular wall networks pulsed nature of ventricular output where oxygen and nutrients are pul as an arterial pressure pulse at various peripheral arteriole and capillaries remains the (from the left heart). aorta pulsatile nature of ventricular output a qualitative measure of neural pathway. initiates blood flow from the heart into the heart) frictional losses in flow reaching the capillary level right from the left periodic efflux ventricles such p486]. [7, p395]. that blood It is at the transferred from the blood to the tissue frequency of nerve impulse activity elevate muscular/neural tone. within a muscle or 1 INTRODUCTION 4 and metabolic waste products are removed and aorta blood has very additional There is only Change in elastic walls which Subsequent diastolic pressure. discharges the blood into the in drop a slight arteriole caliber arterial pulsatile recoil of during eventual The pump function of aortic wall capacitively systemic circulation. arterial Active of due to increased flow systole2 the distended blood the pressure until resistance and is arterioles are reached. regulated regulation of arteriole caliber flow to quasi-steady flow in the distal Timing Mechanisms demand through distend strongly impacts flow autonomic nervous system3. 1.1.3 for blood) from the body. excretion The from the tissue (into the primarily effectively by smooths capillaries. Cardiologic Events the heart is precisely concomitant shifts in controlled cardiac to accommodate beat-to-beat output4 over metabolic shifting and extended time frames. Cardiac tissue has is known [7, as rate of [7, ity rhythmicity node, 2 p399]; the (sis'to-le) is the ventricular filling and hence, systole and diastole to occur. 3The 4 output about thus termed 90 as polarized. is denned of ventricular period relaxation. as and millivolts A 'cardiac the product of the heart value. its function. Internal negative with respect The highest Diastole encompasses on page rate and The potentials to the cell orders of automatic the atrioventricular activity (Figure 2). cycle' is described in Section 1.1.4 rhythmicity a zero or positive cardiac contraction. as tissue to contract, implies that sinoatrial node and importance in regulating autonomic nervous system Cardiac depolarizations is known the tissue type found in two areas, the which are of prime Systole upon normally cells are are of approaches, from the negative, cells are surface to spontaneously depolarize. This property which causes cardiac muscle depolarization depends tissue characteristic the regularity and automaticity voltage potential of cardiac and innate Depolarization, p409]. a cell's an the (di-as'to-le) the is the period of period time for both 10. stroke volume [7, of p534]. 1 INTRODUCTION Superior vena cava Sinoatrial node Right atrium Atrioventricular node Right ventricle / purkinje fibers Papillary musde Figure 2: Schematic from Berne [7, representation of p414]) the conduction system of the heart. (Reproduced 1 INTRODUCTION Sinoatrial Npdq. superior and 6 The the vena cava and receives order depolarizes, spontaneously the cardiac of rhythmicity by or heart's internal neural network into the left atrium, initiating blood from the into the atria Atrioventricular Node. surface at the lower various the node be The slower signal of its the initiate than the natural from the AV myocardium. own reduced p410j. This delay cardiac by the The SA system. p410]. has node associated cells which initiates the impulses through the the across spreading node When the SA stimulation, of neural distally in or right atrium, contraction expels the AV node, located (Figure 2), neural allows second activity depolarization node moves conduction rates on the anterior the spreading differing conduction neural speeds impulse is slightly delayed before for optimal highest should rate of filling order of of the ventricles rhythmicity of all incident impulses from the SA the AV node or interrupted. though the Purkinje fibers from the interventric a prescribed manner per receives due to causing Should incident impulses from the AV frequency (30-40 beats regulated the heart of (see Figure 2). This Normally, node. rhythmicity, the Purkinje fibers The impulse fashion, atrium which possesses also ular septum outward or a radial right The AV node, may [7, between the 'pacemaker' depolarization discharge a atrioventricular [7, tissue, right atrium ventricles. ventricular contraction. cardiac effects in the AV node, the regions tissue electrical atrial contraction The end of in triggering p414]. cardiac nervous autonomic nervous system impulses originating from the SA through of all This depolarization cycle. autonomic chemically induced node effect a the on (Figure 2), is the intrinsic aorta impulses from the neural the highest within SA node, located sinoatrial or can initiate autonomic nervous system. be absent or slower ventricular contractions at minute) than that throughout the node progressive contraction of the SA or AV neural network of than a much node rates the heart can [7, be 1 INTRODUCTION Measurement piration to rate, 7 Physiological Activity. of autonomic effect patient These state of a patient. Normal when possess properties sented as electrical potential changes the skin, of sensor electrodes on This activity. EKG (also ECG) An EKG the ment of electrical waveform labelled cardiac The initiation heart cycle of atrial and timing 100 complex repolarization of is formed by between the and seen to physiologic cardiac tissue and the activity, monitored. tissue skin repre Placement of cardiac electrical produce an electrocardiogram or dependant [7, node as basis, which shoulders right shoulder and as ('firing' and and of number and place typical lead II the SA node) is indicated is the focal The duration The interval dis- EKG5 point of elapsed and is indicates the P- by onset of ventricular in this study for extracting the QRS complex is normally time between the P-wave caused by the delay of the and cardiac The T-wave is indicative of the after contraction. 'triangle' of a the points on a complex which the time between leg the cardiac cycle are common and mentioned previously. tissue upon illustrated in Figure 3. p422]. P-Q the by distinctive is the QRS information. cardiac type denotes T contraction is termed the the the two marked milliseconds beat-to-beat 5The lead is the AV node) of through the AV a recorded certain attributes of P, Q, R, S, as ('firing' contraction the QRS On but The dominant feature between 60 signal activity is normally the the neural for the monitoring allows performed non-invasive methods. body be res signal. electrodes The contraction therefore, can about within resistance, this in the thoracic cavity, signal possesses specific attributes cernable. wave. the heart. Since and conductivity activity rhythm, continuous-time mea information significant neural of cardiac is routinely pressure In particular, can elicit moves across of electrical blood routinely done through measurements are 'wave' and and prognosis. respiratory activity function involves cardiac depolarization the tone, blood chemistry, diagnosis, treatment, surement of cardiac and Clinical monitoring pubic the lower left is region chest. successive used or for the lower left R-wave peaks (Figure 3) has signal measurement. chest. Lead II This triangle represents the path INTRODUCTION 1 Figure 3: A typical lead II EKG marking distinctive (Reproduced from Berne been observed to vary [7, by time-averaged indicator rate many milliseconds. of cardiac contraction. (in beats/minute or successive BPM) can The In The skin Hence, the monitored by stretched. be can within chest R-wave displays most a certain serum often of determined property that cycle. an is simply mean value of changes and expiration. EKG a the time EKG trace, the mean of beats (1) Elapsed time exhibits a brought This effect in resistivity change the Note that often a superposition of chest since both the about by during when respiration the heart pulsates respiration and EKG volumetric changes of is illustrated in Figure 4, which and respiration signals. chemicals, gases, by (MHR) rate the Number these resistivity fluctuations. inspiration levels cardiac be determined from Equation 1. relative expansion and contraction of recordings of actual Blood at from peaks Mean R-R duration due to thoracic impedance during the = the thoracic cavity, there is waveforms the possesses heart mean looking 60 MHRB/W during p422]) duration (in seconds) between heart points appropriate and hormones laboratory assay (including catecholamines) testing using extracted are blood 1 INTRODUCTION samples. 000 3 '000 'a. Figure 4: An . the 1.1.4 The respiration the spontaneous cardiac output at . ee '6.001 '00' EKG EKG and signal 9 * & be . 1 . .1 _ 12.0 1 I '9.00' 'xa'.B1 respiration tracing. that and cardiac _l I is.o 'xa'V Note that 1 I I ls.e 21.0 'is'V '21'. respiration activity (the pulse) is I r e activity is superimposed signal. Regulation ods of normal 6 actual superimposed on on ee and activity levels activity, Feedback Mechanisms of the SA appropriate and to cardiac output AV support is of Cardiovascular nodes is generally basal metabolism. modulated by Activity sufficient to maintain However, during various physiologic stimuli. peri This INTRODUCTION 1 is the modulation part, the within greatly 10 result of a following depending upon biological feedback-control text. The demands the level and type the of body internal of system for affecting the timing, volume, and strength of Information concerning the diovascular activity. information and blood of Blood chemistry includes chemistry. the the gathered endocrine or chemical hormonal feedback-control Cardiovascular and vous system activity. system and gan the is functions responsible include per to car collect body temperature, rate, such as oxygen and other quantities. many carbon Commu These primary pathways. autonomic nervous system pathways and systems performance are directly form a complex neural and network. autonomic nervous system for the subconscious transient physiological autonomic nervous system is influenced during in modulating utilized respiration and that (contractility). called receptors are used Together these system. respiratory The is information involves two primary conveyance stimuli vary must make minute changes quantities levels, hormone levels pH information mechanisms of current physiological state blood pressure, blood volume, about external contractions Various biologic sensing devices dioxide concentrations, nication its oxygen and nutrients and turb homeostasis6. In responding to this stimuli, the heart is outlined, in which is a subsystem of monitoring stimuli. by affected autonomic ner the central nervous and regulation of The function various by drugs, internal or and performance of chemicals, and all of the physiological quantities mentioned above. The The Autonomic Nervous System. two subsystems of distinct neural various metabolic activities. and the internal outside the environment the 7The These two parasympathetic nervous homeostasis: system tendency while [24, of pathways simultaneously which collaborate subsystems system7. biological autonomic nervous system Most systems to interacting are often maintain and the is comprised of and compete to sympathetic nervous system a synergistic relatively adjusting to relationship constant conditions changes originating p584]. parasympathetic nervous system is also known as the regulate vagal nervous system or vagus. exists in the within or INTRODUCTION 1 between the 11 sympathetic and (internal organs) viscera some pathways, only and other areas of by the body sympathetic and parasympathetic pathways. The arterioles but are also innervated Both the impulses ral (resistance vessels) a small innervated the vagus, The heart is primarily innervated are proportion, in the genitalia, by are bladder, large a parasympathetic nerve the only and dynamic internal by various receptors physiological state to in the appropriate control centers significantly to the feedback munication mechanism contributes innervated by organ. 516]. Hence, viscera. sympathetic salivary glands, sympathetic and parasympathetic nervous systems support collected the of sympathetic nervous bowel, [7, organs dually innervated a by by dually parasympathetic pathways, and some are both system Some parasympathetic nervous systems. afferent8 neu communication of is achieved. This the com control of cardiovascular activity. Chemicals the body neurons to assist Different neural of the utilize across Neurotransmitter Blockades. neural pathways a gap (synapse). neurotransmitters pathway synapses. neural blockades directly services. across for 8AfFerent from the stimulation neural or spinal cord. are called synapse the blockades of The spinal the import neural cord at interfere with (neuro-blockers) by the neurons neurotransmitters. the and synapse. normal their Two function effect is to neurotrans are atropine and propranolol. pathways various of the sympathetic elevations sympathetic nervous system increases nerve cells or sympathetic and parasympathetic and chemicals which which are of some adjacent produced and released the each of between impulses attempting to transmigrate the The function in general, brain chemicals synapse are called antagonists or Sympathetic Pathways. extend The are used Drugs Neural impulses travelling through and must often pass in transmitting the impulses impede the mitter and metabolic activity. With impulses travel from the periphery in towards nervous for the different differs respect system organs with some organs to the it but cardiovascular central control centers such as the INTRODUCTION 1 12 system, increased sympathetic stoke rate, The two volume, types for The vessels is 0i /32 skeletal subtypes. receptor contractility, type is involved tant to the current study primarily innervated (blockade) used for by blood with of system extend heart viscera. organs but in cardiovascular maticity [7, general of The norepinephrine. the of the cardiovascular f3r adrenergic blood pressure and rate variability, The The nervous systems 9EfFerent neural in a respon and they receptors. synergistic, and are resistance-type further receptors result work. categorized in increased A vascular smooth muscle. volume regulation, smooth muscle of the and This is impor vasculature is common neurotransmitter antagonist is propranolol. neural pathways of the parasympathetic nervous spinal cord) into parasympathetic nervous system also differs with some (and the decreases region sacral for affected rather by synapses of than impulses travel from the brain the of activity. metabolic parasympathetic efferent neurotransmitter is in a-adrenergic the stimulation system and The investigated in this by epinephrine, muscarinic and a common neurotransmitter antagonist The the eye, of receptors are not the brain system, increased p451]. by muscles of j3\- and /?2-adrenergic synapses The function type is and cardiac conduction velocity. /32-adrenergic directly from receptor different neurotransmitter, is prevalently found in the Parasympathetic Pathways. the muscle, the Simulation 02- adrenergic receptor The each use a receptors are stimulated in sympathetic nervous system contain beta (/?). Each and receptors are stimulated myocardial the stimulation. (arterioles). These types and heart rate, type (a) tissue, they to automaticity, heart cardiac p451]. alpha sites, of rates prevalent The /3-adrenergic into the type different a-adrenergic receptor blood of receptor a particular each react at type [7, contractility activity increases post-ganglionic adrenergic synapses of major sible and efferent9 or spinal cord out to the cardiac auto parasympathetic system is atropine. sympathetic antagonistic respect activity inhibits the is With and manner. the As parasympathetic an towards the body. example, if a INTRODUCTION 1 need for increased increase its crease flow output then decreases its will cardiac output efferent cardiac 13 of neural a only cardiac output without the sympathetic nervous system will impulses. However, If the certain amount. level current Therefore, result. arises, the of efferent act actively opposing the synergistically to The tonic level conditions is the 100 beats Chemoreceptor Influences. portance (low for the oxygen trigger a response account for respiration account about [7, from the 70-80% p627]. with oxygenated alter per minute Chemoreceptors blood [7, The chemoreceptors. of the are an The effects on cardiac response [7, important The physiologic rate of p451]. levels of various chemicals and is directly levels im concentration) both central chemoreceptors carbon-dioxide (in the are of most involved. Hypoxemia carbon-dioxide activity for (in the medulla) induced increases in carotid10 and aortic bodies) p627]. element in the maintenance of perfusion of blood. Autonomic impulses resulting from volume, under and carbon-dioxide peripheral chemoreceptors pressure and overall sympathetic and parasympathetic monitor hypercapnia (high for the remaining activity Chemoreceptors may and has increased the 'normal' pathways, cardiovascular system since respiration concentration) cardiac output simultaneously, the intrinsic heart in the circulating blood. Oxygen compounds further increase in may have opposing If both non-zero). are administered adults averages about and subsequently the brain chemoreceptor stimulation affect autonomic cardiovascular neural activity. 10The carotid sinuses and the carotid in parasympathetic nervous system sympathetic nervous system's action. autonomic nervous system blockades will alter cardiac output. insignificant (i.e. not neurotransmitter young of sympathetic stimulation parasympathetic nervous system sympathetic and parasympathetic nervous systems activity but a activity, normally bodies are near the internal carotid arteries within the neck. 1 INTRODUCTION 14 Respiratory Influences. respiration the centers of Control brain, parasympathetic pathways hypercapnia increase walls of respiratory The the effect of respiration The most as inspiration [7, and which receptors, in the of the lungs pons, through Both hypoxia increases respiration inspiration and rate layer in smooth muscle during the by exerted and impact blood lies in two primarily includes The and expiration. nervous neurological effects the tho include changes Variations in the heart mechanical and neurological Respiratory arrhythmia. mechanical and pressure changes within system. these areas: sinus arrhythmia at rate influences, is is detectable in p456]. pressure Blood Two afferent principle information information is detected pressure Baroreceptor parasympathetic system. arterial activity cardiac performance as a result of sinus respiratory baroreceptor. a the inflation parasympathetic frequency, individuals on Baroreceptor Influences. called called stretch mechanical aspect the of respiration known medulla oblongata chemoreceptor stimulation. afferent parasympathetic airways monitor during cavity in the tone the to response activity is primarily activity. neurological. racic specifically the Mechanoreceptors, and volume. the in of respiration impulses are locations in the and are by conveyed a type of neuron the via primarily cardiovascular system contribute located in the arch aortic and the carotid sinuses. Heart arterial the rate response blood is inversely pressure variations. related This to changes response is invoked sympathetic and parasympathetic nervous system the direction than 20-30 rate). the pressure mm Hg, cardiac When change. sympathetic After which, further increases in in further blood of reductions pressure. A in heart small rate. in blood arterial by pressure within normal reciprocal changes activity, the blood tone is completely net effect pressure pressure elevates parasympathetic The decline in blood opposite pressure affect will occurs decrease for depends increases suppressed in both on by more (lowering heart tone, resulting decreasing arterial parasympathetic tone 1 INTRODUCTION and 15 thereby increase heart heart is solely rate which rate. attributable to Blood Volume Influences. atrial ate (and hence cardiac) the heart blood [7, p455]. invoke this reflex, which pressure Stretch increases in diastole. of change Blood in heart is known the Bainbridge as Vascular Flow Resistance Influences. flow vascular ulating (a neurons and riolar caliber. /32) innervate Increased lation, depending the current pressure (skin) tissue may the need by the the [7, extremities. with the for regulation of volume, vous be autonomic serum glucose augmented or One category drenaline) Subsequent Changes in and of cells in the humoral is (sugar) levels, and hormones and epinephrine by various are the drugs and vasodi imparted due to stimulation increases in linked arterial with and constriction of the blood cutaneous the blood arterial blood above. cardiovascular performance origi normally function synergistically hormones in the and sympathetic in reg regulates arte actually described response activity can Sympathetic pressure. directly the dilation Circulating systemic elements either vasoconstriction body body acceler hemorrhage or vascular resistance often change effectiveness of endocrine of in reductions or the in changes primary blood arterial metabolic activities some of which diminished infusion volume of reflex. The hormones affecting nervous system. many system, the results illicit the baroreceptor glands assorted by arterioles are specific neural or p513]. The Endocrine System. from tone sympathetic by p454]. the degree monitor unaffected vascular smooth muscle which sympathetic regulation of pressure and as a result nate this Thermoregulation result. circulation vessels of upon The thereby affecting resistance is incurred volume changes atria [7, tone sympathetic Increases in blood rate accelerated pressure promote an in both receptors filling during This type rate. Further decreases in include tone. As body osmotic with the on cardiovascular are responsible balance, blood autonomic ner performance can and chemicals. catecholamines which (adrenaline). Epinephrine is include released norepinephrine by the (nora adrenal medulla 1 INTRODUCTION and its marily rate, presence elevates cardiac stroke ways, 16 volume, released and by induces Circulating and contractility, it induces conduction arteriolar dilation catecholamines are used as neurotransmitters reabsorbed sympathetic nervous of Norepinephrine is p979]. pri arteriolar vasoconstriction. is partially the level [7, cardiac neural path Norepinephrine increases blood pressure, heart sympathetic neurons. by the tissue. Excess is catecholamines circulating a is norepinephrine method of by released circulating blood by system synaptic clefts and assessing facilitators synaptic and Norepinephrine which affect autonomic nervous system activity. neurons velocity in sympathetic away from washed hence, monitoring sympathetic nervous system activity. Psuedo- Periodic 1.2 Many continuous-time physiologic waveforms of cardiovascular origin are pseudo-periodic in their nature rest, may [4]. To the observed. Rhythms casual to be appear from for Variations in years. by Hales R-R intervals yield a mean short arterial heart blood an question heart rate logical value. of questions causing the many specified not In observing these a pattern that studies of which to follow involve oscillations. (EKG) time (see Equation 1). Upon may be: 'Is there been the focus and respiration close fluctuations scrutiny which have been are the recorded when However, period pressure electrocardiogram observed over a rate durations. reveal periodic individual R-R interval durations may mean the heart beat as most easily subject of is heart at rate have been known observed as early as 4]. For example, if of for individuals healthy [1, such observer, these waveforms, if periodic waveforms 1733 Variations in Physiological Waveforms be duration, by closer equal to, but to these answer determining of of this the This about, the times, the one question affirmative. of pattern and will EKG, however, the R-R interval oscillations?'. number duration, rather oscillate has been the the type of that time inspection oscillations exists the is scrutinized, division The has next mechanisms 1 INTRODUCTION 1.2.1 Origins of 17 Variability in Physiological Waveforms The human body to maintain homeostasis. This interaction involves of function, system response is is dependent a system which time, and upon significant subsystem cascade- system interdependence, duplication Examples for effects. interaction each are shown below. Interdependence: Release gered of epinephrine by from the endocrine system is trig sympathetic nervous system stimulation of the adrenal medulla. Duplication of function: Release by of epinephrine bloodstream increases the effect (through of the cardiac increased adrenal medulla output, which into the parallels sympathetic efferent stimulation norepinephrine directly release) to the sino atrial node. System response time: Circulating epinephrine requires time to tissue through the systemic circulation cardiac response. The norepinephrine reach before effecting sympathetic neural release) is cardiac a impulse (via received and processed almost immediately. Cascade-effects: Vasoconstriction in the serve heat) may alter arterial invoke the baroreceptor System Behaviour. static perturbations is useful may vary in quantifying time constants, The time required while slow reacting A 'speed blood systems response' of times. Fast reacting systems will circulation (to pressure which con may response. for the body's substantially. such response cutaneous to respond index (time constant) systems will have large valued to homeo- have time small valued constants. INTRODUCTION 1 If a stable is system11 system will react new 18 according to its the time required between the initial level value = Initial + 0.632(Final If is a stable system - system This is important impulses, If is basically quency to function oxygen the of and modulated^2 periodic in the length During of pulse, the reach 62.3% the of change r when = Level metabolic to their such as the may be cardiac cycle activity, many within This this band. transmits neural of system. in nature, the some critical value. a system which system, respond with only to frequencies responds type system will is below pulses only autonomic nervous rhythm rates return of the cardiac of the to expected physiologic rhythms demands rhythm, is body but per compensate increase in fre upon cessation of previous state. one and upon processing autonomic nervous system. change affects stable is dependent The transmission concentration, systems, A frequency the increased sino-atrial node. 11 the cardiovascular system activity. the to first- step-response of Psuedo-Periodic Cardiovascular Variations 1.2.2 their system and settle at some final level (i.e. time elevated a periodic is band-limited condition. support the activity, the is already a small change for the transient by perturbed frequency a a system which turbed, its since the and for the time in the r which exists step-change, the with a say Initial)). sufficient amplitude when implies that the level, nature within some amount of constant in initial an level. For example, the time order systems represents The from perturbed being system carbon-dioxide cardiac the of cardiovascular concentration, activity through being renin- denned angiotensin as a system regulate information is a major Arterial blood pressure, total blood volume, and pH also be system which possessing poles levels nervous autonomic Cardiovascular activity may the to autonomic nervous system altered are monitored, and system stimulation by is involved the of action of other with only in the left half blood of the volume complex S-plane. 12A frequency the modulated pulsed signal amplitude or strength of the pulse. transmits information by varying the frequency of 'pulses', not 1 INTRODUCTION 19 regulation. In maintaining pathways, the nomic the neural impulses the to the sent sino-atrial node or system. The resulting mechanism having and many cardiovascular a reaction by the indirectly by distinct own in about question. by This time. With this cycling in conduits, blood communication the responsible subsystem. The is characterized the of by effects on The results serum HRV but itself, in HRV. This by the endocrine venous blood pres a change culminates listed, in a quantitative Response inhibition is quantity. an overabundance of the quantity quantity, low-high-low. ..etc., the cycling comes of the over physical state of pathways, regulating the activity phenomenon, heart of rate investigation. current Variability work is known variations of HRV is a the as heart elapsed result of rate variability time between communicated maintaining homeostasis. Changes in catecholamines, and respiration other physiologic events make cyclic variation to measured Heart Rate while stimulation of mechanisms with each the items just of quantification of one such cyclic beat-to-beat to the heart blood pressure, For any the through Response to occur. vessels or neural heartbeats (R-R interval duration). perturbations of investigation in this phenomena under which The genesis of Background 1.3 cycling the quantity of the variability, is the a directly blood pressure, arterial a second subsystem which reacts results upon described in Section 1.1.3 these feedback to increase the a subsystem activity auto time. response appropriate subsystem. through 'electrical' catecholamines released circulating quantities, continuously decrease normally induces brought are effected systems either activity cardiac performance reflects its other All the sinoatrial node. Changes in blood chemistry, temperature, sure, which various control mechanisms superimpose to modulating contribute levels, cardiovascular performance in the intrathoracic action perturbs venous rate important pressure as have the consecutive physiological body orientation, most significant contributions. a result of respiration blood return, (HRV) and activity through pulmonary and 1 INTRODUCTION aortic pressure Postural in heart time is affects (standing body regions to up from hypotension. Some required to combat in a acceptable range waveforms the and have revealed a close performance the of developed of its stochastic methods of various studies in sympathetically which restores activity blood of pressure blood electrocardiologic of heart rate blood hypotension. arterial the heart autonomic nervous system activity. for the detection change and pressure autonomic nervous system After system. electrical cluding: [9], have involved a HRV resulting from the interaction nervous systems with cats body by occurrence of orthostatic variations this sense via methods non-invasive Many studies the and variability activity have analysis spectral content. Likewise, pects to redirected the of compensate, this is known not required areas of relationship between to did due to pooling drop would [1, 4], further investigations into arterial into the methods revealed a connection also promotes a modification blood flow is Since the first cardiovascular developed, investigation were time is [1]. cardiac cycle position) in lower preventing the documented in 1733 by Hales the mechanisms Normally, arterioles of in the head pressure amount of it. Related Experimental Work. were a supine if homeostatic stimulated vasoconstriction pressure the periodicity Upon standing, blood rate. orthostatic more modulation, changes blood in lower as 20 dogs the [17, 18], of and rats [3, 21], humans lambs [33]. Focal of species the cardiovascular system. [1, 2, 11, 26, 32], rabbits variety to investigate sympathetic Various species and various as parasympathetic have been studied in [8, 10, 11, 12, 20, 23, 26, 28, 31, 35, 36], points germane to the present study are detailed below. The literature the frequency low-frequency Hz spectrum of band and greater contains a that there reveals large and the HRV are at least two dominant waveform. In humans, the high-frequency band, located Hz, respectively. that 0.15 frequency In normal frequency these bands component which corresponds are approximately subjects, the bands within termed the at 0.04-0.15 high-frequency to respiratory band sinus arrhythmia 1 INTRODUCTION (i.e. HRV breaths of 21 the respiration frequency). Normal at per minute 20-30 breaths Respiratory (0.25-0.28 Hz), Rate Regulation. from respiration, nates hence, through strated controlled several studies breathing tivity. [1] example that suggests renin-angiotensin of one system Orthostatic Loading. lates to blood for pensate perfusion low-frequency is disabled in will result signif been amply demon phenomenon as device) [10, 12, 26, 28, 31]. of autonomic blockades has been done autonomic modulation of cardiovascular ac HRV activity (about 0.04 by chemical Hz) increases blockade in the dog. (disabled) for by increased frequency and tems [28]. orthostatic are action of another when This is in order an to altered in the brain may orthostatic decreased posture to veno-regulation occur resulting gravitational effects hypotension and are com parasympathetic efferent and observed com heart activity fluctuations rate 36]. modulated load and and pressure regulation re Upon standing, these positions results sympathetic arterio- perfusion of tissue ischemia. band (below 0.15 A decrease Without effects, insufficient Several investigations have Low- in origi activity 36]. the brain. body upright [5, 12, 23, 26, 28, 31, 35, load, of gravitational during pensated [35]. activity One important factor involved in blood of consciousness and incurred This Administration compensating for the system respiration metronome or similar changes a respiration rate homeostasis. maintain in loss (via [1, 2, 3, 9, 11, 21, 26, 28, 33, 35, Akselrod the to investigate 2-12 have modulation of cardiovascular cardiac rhythm. Neurotransmitter Blockades. in Partial 15-17 a respiration rate of pl077]. purposely altering icant fluctuations in the basic have and normal children ages (0.33-0.50 Hz) [24, per minute adults of by both the high are mediated Hz) HRV components are sympathetic frequency band (> by the increased by and parasympathetic 0.15 Hz) parasympathetic system orthostatic nervous HRV fluctuations sys during only [28]. The increased 1 INTRODUCTION due to vaso-regulation of the heart Diseases lating rate variability [14, 15, 16, 17], [4], exercise periods in [4], [20], Other and disorders and use of [4], and 36]. bio-feedback specific [23], pediatric [4, 5], re my head trauma methods on patients with re loadings patterns under various in flight test interest in hypertension such as familial dysautonomia components pilots have also been during performed P178]. Cowan following after [10] the shows cardiac a significant to be shown indicated that 15 days an reduction but later arrest bio-feedback training to has been the control indicator after myocardial hertz13 (eq. is in autonomic cardiovascular regulation. the 0.03 eq. peak power Hz results data suggesting [14, 15, 16] low-frequency in are disappeared frequency, Goldstein reduces peak near zero the direct Hz) levels respiration a in to severe 0.08 the data on page 25 for Reductions in HRV power cardiac again arrest. Baselli low-frequency normal control [4] peak loops later determined that became the dominant normal autonomic cardiovascular activity. head trauma pediatric patients acquisition and and HRV an explanation of equivalent hertz. brain that power and analysis writing. See Section 2.1 levels, six months Hz immediately normal delays in the eq. of serum catecholamines and result of rate. power towards large amplitude, Investigations a return HRV HRV, impending infarction, and a peak at power increased representative of indicates that HRV low-frequency of possible 0.03 equivalent in showed at 13 low-frequency have had studies [10]. Investigations into HRV normal adults in increased results [4, 5, 12, 23, 26, 28, 31, 35, diseases diabetes quadriplegics cent cardiac arrest [22, spectra patterns of specific infarction ocardial loading orthostatic Specific Conditions. and HRV 22 injury significantly pediatric brain death [15, 16]. These latter methods detailed in this INTRODUCTION 1 Justification 1.4 This has been research perimental protocols endotoxin-induced to facilitate the and collection and analysis of of Primary study patients in the and the will support bit is percent of neurologic of rabbits for this nature cardiovascular collapse during consideration 14Septic nents of heart shock software package employed of this rate work is a form the circulatory but The analysis based are on head trauma are pediatric (University Rochester Medical of of pediatric each patient served as is two-fold in for power within specific variability injury. The study work [17, 18]. The of septic of not examined in the circulatory action of known function is on pressure [24, is for, neurotransmit using on previous frequency resulting from bacterial infection. It in dangerously low blood methods Based individuals rab rabbit also assessed present work. has direct impact shock system and results [17]. The early detection power are expected within specific shock patients own control subject. endotoxin-induced septic shock septic shock in HRV head trauma their and frequency The New Zealand White nature. and establish non-invasive of, but that data is certain changes The of application software and respiration waveforms. on autonomic modulation of cardiovascular rabbit model studies, development New York). The primary hypothesis involves the investigation an established animal model ter blockades anorexia nervosa. Children's Critical Care Center here to study the used EKG aspect the hypothesis. In this study The study the clinical establishment of a correlation of and with HRV with Rabbits for the subjects Strong levels information found in the literature. Humans Center, Rochester, bands disorder, In head trauma, pediatric correlation of serum catecholamine the eating ex applications. clinical potential have included: protocols specifically designed for the are Use 6hocku, with develop to close collaboration with physicians techniques analysis injury, collective analytic 1.4.1 the and in this thesis is primarily involved Specifically, methods Research conducted septic brain during power of to date employing these vestigations the 23 bands. susceptible attacks pll27]. the to compo 1 INTRODUCTION circulatory infections of the depressed at are also means their immune elevated risk of with power spectra of septic shock Diagnostic use as a might be, physiologic in EKG yet signals or portable analysis unit. often accuracy in with and such patients because surgery patients and abdominal work may lead to effort individuals. and being result of neurologic of considered at injury, heart the heart the cardiovas rate variability rate variability the Rochester Institute in the development industrial accidents, use of such a portable unit. capabilities and perhaps assist specific patterns of Real-time processing may non-invasive Prognostic Tool detected, is currently Severity automobile the to be change. Technology. If successful, this occurs in This AIDS and are several conditions which alter autonomic modulation of system, there associated Cardiac systems. circulatory infection. for the early detection Although there cular those receiving chemo-therapy such as state of Potential 1.4.2 24 of a hospital bedside secondary to head trauma, might be assessed with This may lead to improved in assessing different treatment of modalities. which a certain prognostic 2 METHODOLOGY 2 25 Methodology This section for heart details the data rate variability collection and data formed methods and described supervised mentioned analysis of brain injured changes Additional have been published Early a The brain dead developed Both pediatric patients. The the ultimately function. one clinical and one variability resulting from rate and laboratory studies study involved heart clinical software package software structure upon which physician). collaborating (vS.l) and employed rate study (per utilized the afore analysis variability trial investigated the laboratory endotoxin-induced septic shock in New rabbits. using the developed software, studies performed and [14, 15, 16, the preliminary 17]. Reproductions results of the from the two separate from some of these studies published abstracts of this discussed, have been related work Methods Employed in Previous Experimental Work computational methods enabled variability waveforms derived from gorithms enabled rapid HRV spectral (FFT) power processing frequency specific information physiologic of determinations the data employed methods and autoregressive methods. complex demodulation diovascular is by in developed included in Appendix C. 2.1 an is the base York) were employed package. and in heart Zealand White are New acquisition and analysis procedures were The The ASYST acquisition and analysis. (Keithley-ASYST, Rochester, algorithms processing FFT events of and appears very analysis approach adopted here. short to be data, and by [5]. There in the to be the late 1960s are two duration. Much for from computer al preferred methods of literature, fast Fourier A third method, described useful extracted transform by Shin [32] is spectral analysis of autonomic car work reported in the literature employs [2, 3, 8, 9, 11, 12, 14, 15, 16, 17, 21, 23, 31, 33, 35, 36], which 2 METHODOLOGY 26 (in AUt * I T? ftl.\. n'\ I M * T< I 1 R-R(I> 'l h ^v Figure 5: An series or event series representing R some original rate. an of is EKG most Computing signal (Figure determined15 the elapsed shown recognized duration values re-sampled at signal [4] using a if the i, to process of is signal adjacent detecting QRS-complexes from series, the time sampled R-wave using peaks in Figure 5-b [4]. as an irregularly plotted versus linear, cubic spline, or a constant sampling values as a The interval time. This interval for to function function, sampled waveform of yield equi-time-spaced samples R- between immediately leads R-R interval duration as shown considered rate a constant interval function may be subsequent digital backward step function interpolation [32]. Direct processing 15Given interpolation (c). (Reproduced produce an event which contains from the tachogram, processing method be can to times between R-wave event, in Figure 5-c, In the 5-a) easily interval tachogram dataset the obtained via 1987) Fast Fourier Transform Methods. wave peaks in the EKG (a). R-R interval duration peaks tachogram (b). Interval function from Baselli ft 1, R-R(t) an toT,T,/2. by EKG sampling the FFT period of algorithm T,(T, = 1//,), on both the interval tachogram the accuracy in locating an R-wave peak and the is limited 2 METHODOLOGY re-sampled produced (heart) hertz interval function have been from the interval tachogram beat (c/b). The if R-R variability A power spectrum produced rally to the FFT spectrum is troduced by small process expressed by frequency be transformed by linear by dividing by directly rate used in the as a c/b is the power spectrum expressed as scaling into cycles per an equivalent R-R interval mean much smaller statistical analysis behaviour, of than the without interval mean the regularly time-spaced function datasets. The Along and the dataset. modelling methods is that a advantage is that identification of specific method and Preparation Strong of regularly autoregressive with variance cross-correlation within Human Subjects. An the interval function approach of a preprogrammed sampled frequencies [4]. is The human before being mean datasets as approach involves measures of sam information reveal employing the of autoregressive not a requirement and another straightforward and will not Low-frequency has been documented Study of dataset is of random noise modelling and advantage of components can [4, 5, 10, 20, interfere be detected 26]. Subjects subjects were pediatric Children's Pediatric Critical Care Center. All gave written consent produce in error software used. patterns 2.2 (hertz). The of cycles per second natu The resulting samples. is primarily due to the availability repeating easily using this interval function lends itself for the re-sampling is sufficiently large [4]. This is the auto-correlation identification re-sampled the interval tachogram to of present work and in the algorithm from the Autoregressive Model Methods. with in the results (variance) virtue of the interpolation if the employed ple in the literature. A performed [4]. value FFT c/b scale can may be accomplished scale and appreciable errors is 27 studied under the brain injury patients clinical subjects or at the their families supervision of a research physician. 2 METHODOLOGY 28 The study included 20 patients, 9 brain dead than Individuals catecholamine strumentation, ous blood the throughout To Exclusion the or of one signals Cold of evidence atropine, of and in these 17The or of patients 15 indicates less is indicative cold pressor in the blood less testing minutes test was accomplished but data within healthy pressure and pulse rate, intact the arterial some patients) analyzed encompassed only physiological state previous inhibitors 24 electrocardio (theophylline, hours; mcg/kg/min). 8 A.M. to the myocardium; injury or, amrinone), moderate-dose exoge Since dopamine interfered serum catecholamines were spectral analysis were collected. recording, the response, a GCS carotid of neural reflex which are regulated pathway by the and 3 is the is to artery in individuals of a comatose condition and severe neurologic relies on an (on cardiopulmonary arrest; a measure of responsiveness a normal was used as indwelling rabbits were anesthetized prior pressure independent in was always recorded at anoxic/ischemic but data for blood for patients required mechanical assay measurements, The electrodes catecholamines were obtained after collection prolonged the serum purposes of continu due to the normally changing severe epinephrine continuous-time function. A GCS 7 transducers for the phosphodiesterase ,cThe Glascow Coma Scale (GCS) is score for 4 From existing data (from the instrumentation). All New Zealand White Rabbits. A pressure infusions (dopamine > 10 norepinephrine For to immersion. Serum recent Surface test'7. pressor acquisition. pressor ice- water antagonists nous catecholamine ration. cold bedside monitoring equipment, for data was affixed included criteria administration not measured a twenty-four hour period, human data beta-adrenergic with Scale16 respiratory parameters, respiration were employed since normal reduce potential errors enzymatic or to response from the hand in seconds of a Glascow Coma with electrocardiogram and impedance and tubing physiological ventilation. graphic a pressure monitoring. the last 128 of all and separate pressure immersion by levels, the physiological catheters, for were analyzed lead II EKG source of 11 to 6. or equal standard and was cannulated with neurologic dys smallest possible value. injury [24, used aseptic prepa to p551]. stimulate an autonomic nervous system. increase 2 METHODOLOGY with a pressure the of tube 29 which was connected for rabbit was shaved Collection The human EKG of data recording same and rabbit application of surface electrodes (from the procedures The analog studies. systemic pressure signals were recorded, priate monitors continuous-time depending tranducers. The 78205D in physiologic data acquisition card and to-digital of which ranged mately 4.9 data from module rate include lead II 78213C 78212D, and and central venous experiment, using conjunction with pressure signals were recorded a Hewlett- tubing from the DT-707 terminal board. The DC resulting in a a 12-bit resolution voltage No in-line anti-aliasing filters and appro Data analog- (4096 values) resolution of approxi were employed prior semi-simultaneously18 but the are recorded at a factor of a high sampling respiration and same rate blood to can acquisitions are sequential equivalent to 1000 Hz. for only access each in this a single 'sample' do to hertz 1000 proper resolution reduces the high Post-processing effective investigate the of sampling recorded blood work. channel time-period. rate of not require such a maintain synchronization. studies will the hardware sampling pressure signals 16 to 62.5 Hz. Subsequent filtering a is necessary for decimation digital pressure waveforms and are not analyzed 18Since rate and respiration signal via by using Although . the EKG signal, the the volts specific used signals were recorded or samples-per-second rate the DT-2801-A per quanta. millivolts collected collection. All of to +10 -10 data personal computer equipped with a Translation DT-2801-A data conversion and respi for both the were used monitors models the upon AST Premium 386/25 an using chest of rabbit preparation. blood pressure, intra-cranial pressure, pressure monitor model external pressure for lead II EKG instrumentation) using Hewlett-Packard Arterial Packard blood transducer. The Physiologic Data and respiration signals respectively. an external pressure See Appendix B for further details ration signal monitoring. 2.3 to at Each any one channel's moment, the data actual represents a N-channel time sampling 2 METHODOLOGY 30 For the human patients, 3 from the instrumentation. from recording pressor Glascow Coma Scale patients with samples cold indwelling Serum arterial and were analyzed < 6 was performed on 6 brain dead immediately following physiologic standard at the completion of laboratory data the techniques of blood continuous-time not and collection collected, in the form catecholamines were catheters, by testing data described here (see Appendix B). Analysis 2.4 After collection cessing of stages are Physiologic Data of the physiological necessary prior interpretation. The processing Detection of potential Recording of elapsed Transformation beats per of a computer disk file, extraction of pertinent spectral involving stages QRS the EKG waveform complexes and verification of time between verified peaks the tachogram to an to form variability record filtering Computation of Calculation the information pro and its include: R-wave peaks; an instantaneous heart interval tachogram; rate record of the instantaneous heart rate record in units of Extraction of 'windowing' of and the heart the Fourier transform power spectral the stages into a heart rate containing 4096 points; density of of rate variability record; the heart rate variability record; the Fourier transformed heart ability record; and, The processing data several minute; Expansion/interpolation Digital to to signals signal power within specific involving the frequency bands. respiration waveform include: rate vari 2 METHODOLOGY Digital filtering Decimation to Extraction 31 of the respiration extract and 16"1 every dataset; the filtered point of computation of the respiration Fourier transform for a 64 dataset; second segment of the respiration waveform; and, Calculation the The literature describes and for evaluating the sections Note that the is restricted is performed processing appear Detection Several approaches of diogram (EKG) ASYST software present of directly below. 'scan-window' The employed, select and arranged (arrays), EKG 19The QRS complex steps waveform the [6, 4] complexes [4]. The involved in the data following processing. continuous-time physiological signal analysis original waveform. The analysis of the respi Specific topics relating to the R-wave a in peak Due to the each QRS complex19 of electrocar analysis capabilities of the PC-based blocked- window or array-based approach was used. the QRS in the complex candidate conversion and peak detection method R-wave peaks; the detection developed candidate peaks The algorithms uses a are fixed dis size investigated validity. waveform in the file this file is the QRS in Appendix A. detecting Further, original the HRV of record. QRS-Complexes of further to verify their for the detection unless otherwise specified. signals were considered. to tense, analog on are always processed as arrays cussed within in discussion following 2.4.1 data and to the EKG waveform, ration signal signal various approaches power spectral content of in detail describe, density of the Fourier transformed respiration power spectral as subfiles or referred bears data to as actual in a two-dimensional data file using constructs the integer data file. Each a unique shape the QRS complex, is the are stored item that is being useful in searched integer format a row-column form column of a subfile represents detecting for. in an its location but the R-wave peak, 2 METHODOLOGY a specific channel channel. The 32 from the data (channels) number of columns subfile represents a sampled point fixed 1024 at of 1000 Hz, in the integer data file is the sampling period actual total of each recorded row of a of a subfile rows) (see Section 4.1.1). The Because subfiles. for any one of total the sampling rate regardless of a nominal (i.e. 262144 seconds is therefore dependant channel, information for above for 5. Each and operator selectable and time is approximately 262 recorded between 2 constraints one millisecond Given the number of channels recorded. the is one column in time. The length (number acquisition, but is nominally 256 on each specific board, range may due to hardware rows per subfile number of subfiles terminal acquisition the recording20, sampled points per channel). The first stage data into acquisition voltages requires to their that to of the processing real- valued use of a during was used data file, the the or 'length' 128 each subfile is in size. subdivided Nominally, they analyze. Figure 6 illustrates the processing the of nominal are performed. 'blocks' data 20A rate of occurrence point for possible represents one millisecond nominal recording is done at total the The original integer data raw same resolution scale is then stored and analysis. Since number of scan-windows. used are in size producing 4 , number of 1,024 'blocks' of various the number of 512, 256, usually windows per scan- windows data in points in which each to the 'block' contained within each stage are also shown. The reasoning behind selecting the from the a the the of peaks and reduce occurrences of integer points relative scale of the EKG dataset is number of smaller are the processing scan-windows 256 scale the integer of converted voltage signal R-wave an to utilizes subsequent all conversion of restoration algorithm The into recording, there For a file, for detecting process algorithm is 1024 points, the of each subfile points of subfile. and This original acquisition. To increase the probability 'false peaks', The linear interpolation real voltage is the collection voltages. representative voltage values. another the data after nominal scan-window QRS complexes of elapsed 1000 hertz for 256 in human time, the subfiles with size as 256 patients. scan-window 1,024 points evolves Since is 256 each millisec- samples/channel/subfile. 2 METHODOLOGY 33 II- I I- EKG WAVEFORM: 262,144 Points 256 Subfiles SUBFILE: 1,024 Points 4 Scan- Windows SCAN-WINDOW: 256 Points 1 Zoom- Window ZOOM-WINDOW: 95 Points 1 QRS-Complex R-Wave Peak Figure 6: A Comparison of the EKG to the waveform stage the relative sizes of the data processing zoom-window stage. 'blocks' used from 2 METHODOLOGY 'wide'. onds the For minimum to correlates 34 a maximum of duration between riT11./r BPMmax= this Using is acceptable. signals with excessively /60sec\ \ 0.256 sec/ \ mm The real voltage the careful By operator. threshold value can detection procedure The to be found relate The selected. faster heart of elapsed of time each termined to the the EKG values scan- which of voltage the QRS current later during window is peak, if value by occurring 'too a potential at this per minute (BPM) as If this is not complex in some operator selectable of to the scan- for account rates. this point, signal seconds of prior is signal complex is viewed data, graphically a proper voltage to implementation of value the QRS several global values are using the in all peaks variables are used each scan-window then easily and refers elapsed a sort and indexing scan-window with to, converted a previous the largest to the most recently to the into real index is de amplitude. This is then tested for verified QRS com immediately discarded next scan-window. candidate peak an the temporal proximity threshold R-wave peak, it is the procedure, a candidate peak which time) continues with violated, this Since procedure. bookkeeping peaks candidate peak violates to processed one scan-window at a detection the detected close' peak, processing stage BPM. processing. element of the location of, one exists. of These processed temporal proximity (closeness in plex This milliseconds. threshold value, temporal threshold scan-window, times) recording. locates the represents is the first 20 file containing the EKG implementation relative QRS file containing the EKG scrutiny the indexes (elapsed beginning index scan-window, discussed below. real voltage during As a / scan-window size and all other search parameters are set at are 234 beats =234 r-1 absence of a slower or At this stage, the time rate of / 1 beat \ in the scheme results which windows, by be less than 256 complexes cannot instantaneous heart an maximum in complex occurrence here: shown EKG QRS one only is further as If temporal proximity processed for validity by use METHODOLOGY 2 of a 'zoom- 35 windowing' algorithm. The temporal proximity threshold is value operator selectable. Zoom- Windowing. to verify the T-waves that set. of The the Figure 7 is QRS and the By a valid about 'centering' as the test specified a QRS complex to be detected In the figure, entire at that point L marks milliseconds candidate peak that was is large [7, The p422]. found properly the within during the detected peak, only range zoom- the scan- QRS actual shape and voltage characteristics which the identification by which of actual with an example of search parameters are not 60 to 100 area about the probability reduce being interpreted as from is 95 milliseconds, of employed criteria employed, namely an EKG tracing. the Q-R a scan-window or edge, either R-S intervals, causing Figure 8 illustrates the (Courtesy of the Strong Chil York) EKG record, edge. to is proximity. New either along scan-window and EKG trace if the the necessary large T-waves in Throughout the errors the Figure 7: Example Hospital, Rochester, conducted a representative temporal dren's This is excursion T- waves voltage excursion and of than the duration time formed peak smaller zoom-window complex occurrences will possess discriminate large shows complex centered and window algorithm. complex. introduce detection might nominal size of normal window QRS fluctuations complexes. is zoom-window presence of a spurious voltage QRS A examples occurrence of a slice of left a this or false right, may slice candidate peak 'slicing' phenomena. along the R-S interval by a scan- 2 METHODOLOGY left edge; this window's construction of the a subsequent 'slicing' this by the edge of points the detected cases where number of data points by 95 zoom-window, the from the left zoom-window, the It is peak noted (i.e. points is attempt made at of a timing-error effect After the voltage and excursion compared to fully the is edge at 25 of the within in number subsequent 'last' peak the right few a of a QRS a record. 72, for total of a 95 peak is kept for the processing of as this is illustrated in For a nominal 72 at fully points populated points. be an actual a valid potential the data or to include By design, be located points, (i.e. first window edge phenomena would adjust no peak, invalid peak. eliminates any may impart. zoom-window zoom-window excursion record edge into EKG Although the and/or the voltage is indicative the peak, the true peak, zoom-window. This window was, to find the index location excursion of peak when point at a record edge scan-window might not with a operator selectable large R-wave actual data to the right to include in formation, the points the processing to window 'first' populate insufficient an shifted stage of and a 'valid' as a candidate peak. R in Figure 8). this possesses If the right Since edge. Hanning alignment scan-window or the away from that shifted detected a verified peak L Application complex window that is zoom-window Figure 9 (25+47) of peak occurs near a incorporates the the QRS in the inclusion case results R in Figure 8. If the is kept R) occurrence of a slice addition of an adjacent scan-window detection at point before be detected. would not shifted zoom-window point (point scan-window shown last scan-window), the a sufficient window allows the marks right edge; this to 'zooming'. The This is illustrated occurs. later, In those zoom- of a previous scan-window Point R in Figure 8 a scan-window's scan-window prior to establishing the in the inclusion case results zoom-window. along the Q-R interval prior 36 of is then its largest sorted value. due the depolarization of the as maximum is computed complex inherently complex A QRS indexed, The member. containing the QRS threshold and myocardium. This user-selected value, complex. voltage excursion within the zoom-window is less than the 2 METHODOLOGY Figure 8: A QRS edge slice of 37 complex sliced the Q-R interval by a scan-window edge. and point R Point L marks a left marks a right window edge slice of window the R-S interval. Adjustment for 95-Point R-wave Peak at 25 Points Figure 9: A QRS Zoom-window Zoom- Window " complex adjustment detected to include 95 near the points is 'left' edge necessary. of the first scan-window. 2 METHODOLOGY the candidate the a 38 is discarded peak maximum voltage excursion and in the final temporal proximity test is temporal proximity is peak counter is incremented. continues with the here, the index (index global Otherwise, using the same candidate R-wave referenced the detection during verified R-wave temporal proximity of slow Zoom- candidate peak all the scan- peaks verification When analysis during candidate zooming complete. entire EKG 262144]. The transforming 21This is the name is the a window. If the threshold value, value as is before. If promoted record is discarded during start) and to valid and the processing peak redundant, there (using scan-window), proximity. scan-window peak each scan-window except for zoom-windows this array to a the are actual syntax used detection violation). phase has However, due to the validated complex detection post- millisecond sampling period R-R interval duration (without curly placeholder and enhances braces) to the appear as: becomes the the indices start of the [3, 900, 1923, obvious here in values. in the developed identification phase of contains peaks with respect {Peak. Indexes} dataset may represent The fact that above. the detected R-wave For example, voltage- when a candidate peak (for temporal proximity have been processed, the QRS of cir 'wide' a detection phase, that the temporal are validation. window stage usefulness of necessary signals violate the seems Indexes}21 The resulting array, termed {Peak. specify the location record. for tests described which ..., actually detected in the all scan-windows is peak will occurs once rate the secondary was not violated windowing is discarded not heart in the immediate decision for bearing no peak scan- next scan-window. after zoom-window alignment and threshold next threshold to the EKG Although this secondary temporal proximity test cumstances the continues with zoom-window meets or exceeds performed not violated recording its by status processing program. of variable names. The period within 2 METHODOLOGY Creation 2.4.2 The of construction of the HRV Signal from R-wave Peak Location Data the HRV several steps outlined of array by dataset of elapsed (N beat. The 1) mean actual the times between peaks can 2, is rate period steps are be constructed number of intertwined because equivalent to the from the {Peak. Indexes} detected interval tachogram points represents an heart index locations array involves software used. N is the where peak program, many capabilities of evaluating Equation of from the R-wave signal below. In the the array processing An array 39 and peaks. has The resulting units of seconds per this interval tachogram mean of array. PI{k Tachogram(fc) If this tachogram array is beats per minute. PI{k) (k , to converted termed the instantaneous heart units of +^q~ = This is the time-averaged quantity rate {IHR. beat Values} Values} After rate The and seen R-wave IHR Patching. Figure 10 displays at points for this EKG A 9 and the heart B subjects, further processing to some of exclude the which has heart rate were caused shape and the detected peaks spurious peaks variation an example rate about waveform was about these dataset by 1.5 the in heart {IHR. mean anomalous R-wave Values} heart rate. fluctuations peaks. The volts. strength of might not is (3) 1,2,..., N-l) = volts and were selected as Due to the variability in the from different study peaks and scrutinized. waveform of about maximum (k visual representation of steps, mean a dataset. ttt, periodic variation of in the figure EKG be inverted, be formed Tachogram() 1) above available and can original normal the two illustrates the 'glitches' in the Tachogram (k + completion becomes dataset - = can (2) N-l) ..., then and 60 IHR(*) 1, 2, is indicated in Equation 3. The {IHR. the or array process of minutes per = the EKG be actual signal R-wave sometimes necessary. This 2 METHODOLOGY stage processing as any occur, to remove 40 involves visual of {IHR. in Figure 10, {Peak. Indexes} is the points reconstructed. contributing to the Recall that R-wave (i.e. contributing) Figure 10: Example glitches at points lee. inspection A peak indices B are the spurious Values} for by interval and represents one of computer processed and processed in {IHR. each element Values} the IHR.Patch value and {IHR. If procedure Values} is derived from two is adjacent R-R interval. instantaneous heart result of glitches spurious occurrences. in the EKG rate (IHR) dataset. The signal. -i- x0 80. a 60.0 -- a 40.0 -- ee s 20. 0 . -- 000 ' ' "* .000 16*. 0 321. 0 TIME Figure 11: Example IHR.Patch algorithm. of computer ' 481. 0 641. 0 <s#o) processed ' 801. 0 xEB IHR dataset after application of the 2 METHODOLOGY Baselli 41 indicate that R-R variability is [5] normal sinus rhythm. The 20% value rate, the of not median the mean heart does. This is done to selecting the the to adequately this type eliminate 'remove' of 'salt filter to ber the intervals, M, (2fe, in value, causes a rate for varies variability to produce some positive and pepper function high degradation noise are while expected, value appears corruption. Note that process IHR.Patch is and operator in Figure 10 shown Baselli by the and the Such method an approach in a stage Fourier the on is A:) not of event number grey or low, of the image about the digital current clarity. is analogous to use of removal involves the fast Fourier transform Values}. subject a of time of frequency (in a power-of-two num and since studied, M function problems exist with function Second, is necessary the number of will not at R-R necessarily be this data processing (R-R interval). image, grey Three coefficients as a by the utilization scale may include the signals22. integer depending widely problems are resolved either 'patching' dataset, {HRV. Third, {IHR. Values} a Values} automated by as from {Peak. Indexes} method requires equi-time-spaced samples. but rather, 22Salt dataset removal of six points an alternative from digital algorithm a power-of-two. All three blind, value used Values} An upcoming processing the heart First, in the data heart median in the dataset The 20% tolerance via a is nominally determination in {IHR. rate of dataset is illustrated in Figure 11. noise of points stage resulted pepper' using the FFT Hz). {IHR. original remove anomalous values. and of points the implemented, not data heart mean the uses spurious values mean. The tolerance Values} HRV Dataset. (FFT) to the valid peaks. Processing resulting {IHR. median criteria spurious values equivalent removes processing IHR.Patch algorithm, a influences from any Since few procedure for the of point exclusion remove spurious occurrences without extensive therefore may Although This rate as a reference value effectively be of error selectable. {IHR. Values}. of 10% order of for contributing criteria utilized reference value. median will the on of an say, can scale values interpolation be in algorithm to yield 'spikes' represented a region of as anomalous the image. This 'noise' 2 METHODOLOGY another with a array in real to control time samples. 42 fixed length 4096 of The points. described in Section 2.1. The interpolation as the time spacing that such each new Linear interpolation between approach was considered 'times' but expediency for a non-linear {Peak. Indexes} method uses array index represents equi-time-spaced in {Peak. Indexes} is working is algorithm employed used. A cubic spline prototype program precluded this option. The dataset which produces a but is ations processing begin actual interpolation {HRV. beats algorithm per Values} on page subtracting the temporary dataset beats centered about zero which always contains units of by is described 4096 minute, In the {HRV. Values}, from the {Peak. Indexes} same magnitude of vari This dataset is in the heart processed with the necessary form for FFT the variability dataset rate This resulting dataset is termed {HRV. points. Values}, has analysis. Note that to the interpolated interval function discussed in Section 2.1 (4096 pts/262 sec). {HRV. original Values} extracted fewer points EKG the HRV Dataset is digitally of about 2 Hz. The 1000 hertz). cardiac 15.6 hertz sampled above use of and dataset, frequency the = describe (4096) filtered from the HRV with rate were recorded points HRV In the activity results frequency is process over for the to the unrelated of same reduced represent creating duration. HRV dataset to the sampling waveform. of spectral content contained nents above of sample Note that this uses an effective cutoff context (i.e. HRV frequency a sampled the seconds much Thus, only in rate the contains EKG acquisition, nominally 262,144 approximately 262 tion is result heart 25. original rate of to above Power Spectral Analysis 2.4.3 that per minute. and represents equivalent mean of a then 'windowed'. Before the Blackman smoothing filter is 5 Hz. The meaning described sampled in HRV datasets the 5 Hz spectral cutoff of this cutoff HRV frequency. frequency mainly employed which frequency Early revealed no significant informa the valid investigation frequency smooths is compo 'sharp edges' 2 METHODOLOGY 43 resulting from use of a eliminates noise present. window is any the and and rather To to the HRV applied The filtered linear 'windowed' HRV variability in the converted23 ranging in to a single-sided frequency magnitudes component equal have units of of The in {PSD. Array} is of particular frequency interest located band total and power bands range of each 'For and example, The length 4096 of a nominal resolution, 262.144 (A/), Finally, points information current study only of and > 0.15 respectively. deemed operator selectable. the heart The by represented discrete and a frequency line or bin the Fourier of performed. Hertz. the heart rate variability band-specific powers two frequency bands and are termed the low- are power contained displayed in The report bands to one sided spectrums. hertz in each form. Other number of approximately 0.0038 in these component computations required two to dataset frequency of each frequency necessary. conversion of second record yields Hz, Total the largest / when previously, there amplitude of details in is conversion BPM2 0.01-0.15 Hz 4096 of point density dataset, {PSD. Array}, is powers are computed and mathematical HRV element are expressed as when dataset a 2049 a contributions of a time24. mentioned be investigated in sampled Each dataset spectral content As at to one-half the frequency to the in results conversion results indicates record density useful frequency-band is 23See Appendix A for 2 Hanning a (see Appendix A). process a also The Fourier transformed HRV dataset is per minute. line' spectrum, the band can hertz) high-frequency band, in the and ratios of frequency the The power spectral and power ratios are evaluated. band, leakage effects, has but algorithm magnitude and phase spectrum of waveform. the total power spectral Band-Specific Powers. contained beats 'spectral to the inverse the two-sided spectrum. in {Smoothed. HRV}. units of bands, the smoothing the FFT algorithm with from DC (zero transformed dataset into the The after dataset, {Smoothed. HRV} EKG original magnitude and a phase is interpolation element values represent equi-time-spaced samples. complex values which represents a the cubic spline minimize potential spectral dataset Processing {Smoothed. HRV} rate than spacing. and obtain 2 METHODOLOGY band-specific these The the power powers and ratios contained power spectral frequency bin, indicating 44 within densities A/. This is the lower a is the final specific frequency that band over expressed stage of and in Equation 4 edge of a particular band the data band is processing. then multiplying itow is where ihigh is and from summing obtained by the the index the index of of the width of the {PSD. Array} upper edge of the band. ('high \ J2 {PSD.Array}(n) Data processing required to variability in the originally 2.4.4 second a composite segment algorithm The decimation This partial unnecessary 5 Hz and procedure record original provides computational is included in the those peaks The to FFT analysis simultaneously filtering point frequency complexity. prior digital 16t/, every sufficient Hanning-windowed of the heart rate now complete. dataset is respiration performing extracts is information and and results resolution reduced selected and processed decimation, in (A/ = concurrently. point dataset. 0.016 Hz. without 4096 a dataset is Blackman filtered and power spectral processing. software for direct allowing visual comparison of by display of at A plotting the HRV the respiratory and frequency derived from HRV data. Statistical Analysis 2.4.5 Data the waveform (4) Verification FIR25 process respiration spectrums peak and of spectral content EKG recorded Respiratory Frequency A 64 the obtain A/ comparison gation t-tests, between involved mean, Mann- 25Finite control and standard Whitney U test, impulse response (FIR) study deviation, and subjects standard in the error, are brain injury paired and unpaired the Signed Rank test. digital filters clinical described in detail Due to the large by Ziemer [38, investi Student's range pp387-407]. of values encountered This essary. the the with of processing study the HRV data University was performed by was employed when nec the Department of Biostatistics at Rochester Medical Center. laboratory analysis of (1-10,000 fold), logarithmic transformation statistical University The at 45 METHODOLOGY 2 of involving and was sepsis likewise in the rabbit model utilized similar statistical performed Rochester Medical Center. These those described by Shannon [31]. Appendix B by the Department statistical elaborates of techniques in more Biostatistics are consistent detail. 3 RESULTS Results 3 The from the results ogy section, The which encompass pediatric principle evaluation of autonomic power. colleagues at the of between brain the used of in and with plasma Score, collaboration Children's Critical Care non-invasive heart with Unit, the rate detailed. are those detailed in Glascow Coma Score levels in at patients time and additional several acquisition and section. blood pressure, admission power spectral brain death following spec Goldstein, study, heart of establishment Dr. Brahm Methodology mean tool for the variability Rochester Medical Center. The primary for this study catecholamine of a and severity Table 1 lists the age, sex, heart rate, respiratory rate, Glascow Coma are sepsis, pediatric patients and injury conducted Strong University analysis protocols and rabbit the Methodol Injury Patients research was Associate Director head trauma tone in brain injured correlations This investigations described in hypothesis involved development clinical developing tral clinical and experimental Pediatric Brain 3.1 of 46 compared data to those Glascow Coma Score < 6. Individuals catecholamine for were analyzed levels, electrocardiogram to a response and a cold and respiratory parameters, Results test26. pressor are serum tabulated in Table 2. Figure 12 illustrates the with Glascow Coma Scale herniation graph, it with the and can of brain death. be seen changes that 3 (top), in the blood test narrow relies on an pressure and pulse and Noting use of a mechanical ventilator. cold pressor power spectral rate, the the two a significant brain death. The very 26The in high intact same patient points decrease in frequency Normally, density which are regulated brain-injured 24 hours later marked as LFP peak amplitudes peak this HFP neural reflex of a the after cerebellar and in the top is much wider and is used to HFP on each (i.e. power) spike pathway by (HFP) patient plot occurs is due to (i.e. covering stimulate an autonomic nervous system. increase 3 RESULTS more frequencies) Figure 13 of 47 the when shows patient temporal changes brain death. Note that the 3/3 patients with Figure 14 development shows temporal patients with (NE) levels (E) levels become brain death. the catecholamine (pg/ml) during in Figure 13. same patients represented and epinephrine with rate power approaches zero plasma catecholamine of the development in almost The third the Note that non-detectable patient was receiving assay. New Zealand White Rabbits 3.2 Results from 10 and in changes total heart during brain death. and the development dopamine that interfered rate power spectra low-frequency brain death for the of spontaneously. in heart tonsillar herniation plasma norepinephrine in 2/3 breathes anesthetized adult male rabbits internal jugular minutes after (1.5 mg/kg) mean, [blood] the was vein were cannulated above procedure was infused and pressure (MAP) were unchanged by a over a six minute period. and and tracheostomy The was endotoxin Statistical data carotid performed. (1.5 mg/kg) analysis t-tests. After endotoxin, low-frequency power (LFP) the infusions. in Table 3. The shown performed, E. Coli deviation, log transformation, standard is high-frequency artery Thirty or saline consisted of mean arterial decreased. Catecholamines levels power (HFP) decreased in both groups of animals. After administration of low-frequency that HRV a concurrent power the endotoxin, is indicative increase in circulating a of decrease in impending mean arterial septic shock catecholamines is blood in the not evident pressure and rabbit. between Note endotoxin and control groups. 3.3 Software Application Illustrations of dure using this the graphical output and numerical results application appear from in Appendix D. The data a normal analysis proce represent those of a repre- 3 RESULTS Table 1: Age, 48 sex, Glascow Coma Score, basal spectral values and plasma catecholamine cardiorespiratory parameters, heart levels (mean S.E.M). GCS < 6 Brain Death N 11 Sex 5 M Age 5.9 1.4 6.8 2.2 Admission GCS 52 41 GCS 51 3 122 9 127 11 26 3 15 2 84 4 74 9 on Heart day rate of study (bpm) Respiratory rate Mean blood pressure (bpm) (mm Hg) Low-frequency heart rate amplitude Low-frequency heart rate High-frequency heart Norepinephrine (pg/ml) Epinephrine tp < 0.02, GCS = total rate total power tp < 0.03, < 0.001 Glascow Coma Score 8 M / 3 F 0.01795^ 0.00406 (bpm2) 0.04089 0.01456 0.00047^ 0.00024 (bpm2) 0.01127 0.00342 0.0008lt 0.00049 712 *p 4F / 0.04125 1987 (pg/ml) 9 1.22264 (bpm2/Hz) power power 932 258 (N=5) (N=4) 108* 21* 28 8 (N=10) (N=10) 3 RESULTS Table 2: 49 Cardiorespiratory, testing. Data cold pressor power spectral and catecholamine changes < 6 GCS < 6 + N 3 (years) 3.6 2.2 HR (bpm) 132 28 Brain Death 133 5.1 2.9 28 137 cold pressor 6 6 - Brain Death + cold pressor 3 Age and after S.E.M. expressed as mean GCS before 15 - 137 15 RR (per min) 32 9 38 7 17 3 17 3 Mean blood 88 15 88 17 67 10 65 9 0.06463t 0.03486 0.00022t 0.00024 0.04874 0.01223 0.00005 0.00007 0.00603t 0.00573 0.00097t 0.00097 0.00087 0.00145 0.00075 0.00074 4221* 4318 103* 135 (mm pressure Hg) Low-frequency power (bpm2) High-frequency power (bpm2) Norepinephrine GCS 0.0001, = 3200 (N=3) (Pg/ml) tp < 2992 *p < 0.05 Glascow Coma Score 16 30 3 RESULTS 50 4.00 T SEVERE BRAIN INJURY GCS 3.20 - 2.40 " " 1.00 - - 0.80 " 3 = " a00 0.40 *- BRAIN DEATH GCS 0.32 - - 0.24 - - one aos - - LFP - HFP 1- H 0,0 1 1 I 0.4 0.2 Figure 12: Changes in and GCS=3 power spectral (top) and the density h ae FREQUENCY patient with 3 -- - 0.00 = of same patient 1 1.0 (Hz) HRV in a four-month 24 hours later brain death (bottom). Note lOx difference in 1 as old brain injured after cerebellar magnitude of the Y-axis herniation scales. 3 RESULTS 51 0.08 -, o Patient 1 o 0.06 ? - Patient 2 -J < H Patient 3 < z til 0.04 - 0.02 - .o w c u OS fa I o -J Figure 13: 0.00 Temporal changes in heart brain death. Low-frequency total heart tonsillar herniation and brain death. rate power spectra during rate power approaches zero the development in 3/3 of patients with 52 RESULTS 3 = 3000 Patient 1 a [NE] [E] Patient 3 Figure 14: Temporal opment of almost patient changes in brain death. Plasma non-detectable was receiving in 2/3 plasma catecholamine norepinephrine patients with (NE) levels dopamine that interfered with the [NE] ? [El (pg/ml) during and epinephrine the development o of (E) the devel levels become brain death. The third catecholamine assay. 3 RESULTS 53 Table 3: Changes in various the New Zealand White physiologic parameters rabbit, (mean Basal 146 rate in endotoxin shock S.E.M.) Control Heart resulting from 60 13 Endotoxin (N=4) minutes 18+ 179 Conditional? Basal 20 159 (N=6) 35+ 224 (bpm) Mean 85 arterial pressure (MAP) (mm 5 77 2 82 7 62 5+ Hg) Log Low-frequency power -4.78 0.89 -4.13 0.724 -4.85 0.93 -6.35 -2.78 1.16 -5.40 0.97+ -3.90 0.90 -5.33 1.98+ (Log bpm2) Log High-frequency power 0.73+ (Log bpm2) Norepinephrine Epinephrine Dopamine (pg/ml) (pg/ml) (pg/ml) +p < 0.05, ^Decrease in 127 118 114 91 92 40 111 45 21 0 21 0 28 17 26 8 41 0 54 16 50 22 66 59 MAP > 20 mm Hg 3 RESULTS sentative control data listing, The The menu New Zealand White developed overlay design structure during in the are this A cover illustrating summary sheet, possible allowed a work was structured modular design for the The detailed structure, in menu numerous section. frequency band form and employed future of the additions. processing, analysis its operator and an explanation of included in Appendix E. The processing details Methodology a output, is included. which allowed modular changes and potential and graphical output stages. interface, rabbit. and several graphic plots software a program 54 software are explained DISCUSSION 4 55 Discussion 4 4.1 Acquisition/ Analysis Hardware Requirements 4.1.1 Different hardware during actual data was utilized development the A listing of from stages These differences did require special precautions when application environment. shown during collection and analysis. difficulties but did is Software Development the not what was employed introduce software was the different hardware significant introduced to the used and pertinent quantities in Table 4. Table 4: Hardware used for development versus actual application use. HARDWARE DEVELOPMENT CLINICAL APPLICATION Personal IBM PS/2 Model 30-286/10 AST Premium 386/25 2048 bytes 2048 bytes Hewlett-Packard Think Jet Hewlett-Packard LaserJet II Data Translation DT-2805 Data Translation DT-2801-A 2.5 1.25 computer Hard disk cluster size Printer Data D/A acquisition base card (D/A) card resolution Data Translation DT-707-T D/A terminal board The development of the EKG was and development of of the software respiration it developed, was signals Hz for 5 perform progressed a data in of the stages High of software the stages. As each additional procedure master/controlling to minimize were program. In the early produced, but in potential operator later error development involved creating the data rates were required hence, data Data Translation DT-707 and during (i.e. 'idiot-proofing'). software acquisition channels), were added microseconds acquisition and subsequent analysis the algorithms, only necessary functions implementation algorithm. to incorporated into final versions, safety features The first microseconds were transferred for acquisition multi-channel acquisitions directly to a (i.e. 5000 hard disk file. The ASYST 4 DISCUSSION 56 for this software package employed directly acquisition The layout to the target disk 2.4.1, the acquisition data cluster size is 2048 bytes (2 the allocation meant the reason that 1024 disk file and in five, Disk file data single-precision of the storage for data a nominal integer format in original integer hardware utilized, the disk smallest allocation unit in integer for a multiples Numeric data resulting from the data which used one allocation unit of 1024 recording requirements is the As to be known. the storage of acquisition was performed subfiles used was for procedures and needed present size and were represented as columns size requirements Table 5: during values were contained the length between two in (i.e. 2,4,6,... kilobytes). unit acquisition process was this for data subfile size used kilobytes27) disk. Data transferred to disk of important was hardware dependent. For the was built-in several disk file. computer structure of in Section mentioned work possesses of 256 channels subfile structure. subfiles is for D/A integer data for per value, 2 kilobytes. This Multiple values. in the two bytes shown A was recorded, listing of in Table 5. nominal 256 subfile recording. Number It was storage sufficiently large for Channels directly and on 1,050,624 3 1,574,912 4 2,099,200 5 2,623,488 medium, introduced 1024 bytes. data to timing the hard disk contains of a and errors (bytes) high capacity Bernoulli cartridge, the was not practical since storage and subsequent processing. 27One kilobyte Required Space 2 found that direct transfer intended data recorded of in the Bernoulli disk recorded access data. times Thus, data then later transferred to the Bernoulli The data transfer rate to hard disk was were was cartridge determined 4 DISCUSSION to be by sufficient for Tektronix a To all expected acquisition rates and was verified model CFG250 function in the development aid Packard monitors, of 57 models test The bandwidth signals. determined to be was noise, Analyzer model 3562A satisfy the allowed an Sampling accuracy also were obtained on signals 480 hertz about of 1 0.5 with Nyquist the loan in distorted later processing use of a of locating due to sections included signal only in those EKG from a University volunteer environmental and as line Hewlett-Packard Systems from Hewlett-Packard. The rate sampling of 1000 hertz to 960 Hz. The 1000 Hz the R-wave peaks rate thus in the EKG records without anomalous voltage patient movements. because algorithms loan from the recorded directly frequency milliseconds preserved or which in selecting the a were Hewlettalgorithm, two of its inherit The 1000 hertz one millisecond period. sampling QRS Complex Detection 4.1.2 Some simplified 78212D, these signals, of theorem for fluctuations (i.e. noise) value QRS-complex detection Physiologic resulted This accuracy is signal. and signals supplied generator. which was obtained on determined bandwidth assumptions processing. in the The fiducial nature of understood ends after constant to initiate P-R interval three of the with for the duration EKG with of 'firing' of the of the sampled at program was cardiac the R-wave cycle since the by were [22, p59], the mean determined to be peak. cardiac the In The cycle P-wave, remains under normal conditions. Rompelman 1000 Hz held throughout the is that the P-R interval recorded signal by the waveform were the SA node, indicated assumption made the P-R interval of an for central region the T-wave. The the constancy the derived HRV point searched R-wave is actually in the of 78213C Rochester Medical Center. the of test by is and relatively testing of differences in the zero with a variance milliseconds. Since the EKG sampling rate used in this work was 1000 Hz, the accuracy in locating 4 DISCUSSION the R-wave this the SA msec, in the node SA the eee , Figure 15: An results node 3 . is 3.5 point in 6 For milliseconds. P-R intervals less than the was was performed held. Including cumulative error a mean heart rate of ee 9 . ee 12. e is. e is.e 21. e 5 26.5 29.5 32.5 35.5 38.5 41 se.e 53.9 56. e 59. e 62. b 4 76.4 79.4 e 44. e 47 61 . 4 64. 4 67.4 example EKG . locating (3.5/750) one-half of one percent 23.5 . the 80 BPM (750 29.5 41 in for in time. point . of Rompelman, a mean error of trigger ee No testing P-R interval constancy the P-R variance from triggering period), this milliseconds. above assumption of error and locating 10.5 peaks was work since detection 58 e 73 waveform . illustrating anomalous occurrences in the second panel. Tlie final QRS-complex detection from the an earlier form. The original same current sort/index method proximity ings reduced of and voltage excursion the original movements) to be version for algorithm described in Section 2.4.1 bad form to locate employed QRS a single complexes. validation of candidate It R-wave as valid R-wave peaks (see Figure 7 window peaks. The shortcom and glitches on page using temporal also utilized large T-waves mainly involved allowing accepted scan- evolved 35). (patient Another 4 DISCUSSION 59 3599 xEB 3399e 3999 -- 2 5 99 -- r-A] 2999 1599 lee pe.kA -- -- %i I l I 3.1,4 3.L,: I I. 69 3TT&8 XE4 Figure 16: An problem was the improper identification discussed also scan- windows previously. before confirming a the Patching marily due to of More Method. patient Anomalies complexes these reliable of an example 'sliced' 'sliced' was This with such as those which in the this example {IHR. panel in Figures 16 2 of 34 addition was R-wave peaks sometimes also in the the was can 17, pri due second panel of Values} dataset, seconds and % and Figure 15 adjacent during data recording, shown at ss combining implemented. is anomalies are shown shown of of valid still occurred phenomena edge, complexes near and at the technique identification EKG tracing. a scan-window (muscle twitch, cough, etc.), but derived. The examination, by QRS Concurrent complex. Spurious transients movements in Figure 10 (page 40), closer QRS in zoom-window approach was adopted and Figure 15. This EKG is the trace from for seconds the introduction spurious cardiac electrical activity. enlarged 34 observation of detected the 'zoom-window'. obtained when to The window edges prompted concept of IHR anomalous point at % shown 40 seconds, respectively. be identified immediately 4 DISCUSSION 60 40051 peak C 3209 E0 2899 -- 4B396 2499 2999 16 89 D peak -- 41166 peak -- -- 1298 89 I ^ I 4.1,5 1 4.k3 ^^9 4.21 xE4 Figure 17: An data recording after that time to accept transients in the algorithm shown anomeous point at = by the data dataset inspection visual be 18, illustrates the of the data. in an example EKG Judgement would with a new recording. removed later during described in Section 2.4.2. An in Figure seconds it or replace would 40 extraction of the two effects Smaller tracing. be made at or unnoticed the processing by {IHR. (from Figure 10), anomalies Values} the IHR.Patch in Figure 15 introduce into the IHR dataset. 4.1.3 The Respiration Signal Analysis respiration spectral able. density The greater reason frequency of the HRV is that than 0.15 Hz prompted can usually be identified dataset, however, subjects and the development finding breathing the true of a procedure on a graphical confirmation by display to extract the alternate means spontaneously may have respiration of frequency a is desir broad band may be difficult. the dominant respiration power signal This frequency 4 DISCUSSION 198. 69. 61 -- ^sto I 3"sti I Figure 18: Extraction from {IHR. in example EKG waveform. iste Values} I slt~e dataset 1 lt~e illustrating ' Tile effects anomalous points DISCUSSION 4 from the The heart respiration signal recorded with analysis of directly from the However, minute The rate of as large as a 4096 The mately -70 dB Figure 19 was and to 16,384 These in the high-frequency digital filter the 1000 Hz. being 262,144. from the data of points from the point This per reduced-point and possessed an caused a problem. had original signal dataset if the at number sixteenth dataset. point obtained over-sampled seconds of respiration This, however, noise every its be 20-30 breaths in the reduction re-sample a yield a order of being was recorded was of significant components original would respiration frequency have introduced dataset respiration signal was processed with subsequent extraction of every com 16</, were by a simply finite im point resulted dataset. at of the digital filter include 30 Hertz. This sampling cutoff rate of the FIR digital filter 62.5 Hz for the used was respiration signals ture detail the derivation 129 28Decimation here implies which would appear as the and the position. were recorded directly, from EKG called a removal of sampled values sampled at a lower frequency Sampling the in rate. of approxi theorem for the reduced-point respiration index electrocardiology to have been satisfies points of respiration signals a concept of scalar a cutoff rate and frequency as coefficient value plotted versus Although the involves line 480 Hz. (FIR) effective of to second segment of parameters intended length point content signal the on could recorded, that were is children the full 262.144 reduced-point decimated28. A 64 pulse response points for frequency activity the EKG respiration 62.5 Hz. environmental and abasing into the in 262,144 of respiration points as The intent here order. sampling ponents data frequency of respiration in The signal. Thus the was representative of effective signal. differed from that for EKG processing signal normal respiration rate dataset original recorded 0.3-0.5 Hz. standpoint data the same number of the or appeared the respiratory the EKG variability in that the fundamental respiratory rate Hence, 62 dataset. The coefficient values shown methods signals [25, found in the litera 27]. This electrical axis of an ordered in fashion to approach the EKG result in a signal. dataset 4 63 DISCUSSION FIR 0.035 -| D igital i F liter Coefficients i i i i 0.030 f + + + + QJ 0.025 - ro > 0.020 C QJ 0.015 - U 1 Lu- 0.010 - Ll- QJ o 0.005 \ - "0.5 dB Stopband Ripple: "70 dB_ Passband Freq.: 10 Hz \ - W -.005 1000 Hz Passband Ripple: + t - u 0.000 Sampling taps Freq.: + Stopband Freq.: 30 Hz + + + + + + + + + + + + + + + + + + + 1 % -1- - H 129 Length: J$\_ - i - 1 I 20 40 60 of FIR digital filter 100 80 Coefficient Figure 19: Plot f- 1 h 1 1 120 140 Index coefficients versus coefficient index. 4 DISCUSSION These latter employed in the from interesting methods were a signal standpoint processing but were not current work. Application Features. 4.1.4 The 64 itself lends itself to software application efforts as are through the The display completed at Many error- point that in listing of useful during would and the the the enables listings graphical the with useful allows space the below. steps processing and reprocessing have hopefully eliminate, interrupt the analysis data of data using at differing data. to be include: file performed without deletion, exiting file copying, and indicated. display immediately is facilitated which contained processed operations operations disk free utility that This is especially of basic DOS Those DOS application. directory A which allows crunching data. file, analysis parameters or re-examination of 6uch A file utility given occur which would disk a program which included to minimize, This analysis. the features is indicating of processed retrieve, with simple number analysis. normally loss possible store during Interaction procedures are operational errors A capability to text. maintains an area point any checking process and result any previous displays. A use of menu main menu been any described in than much more after of all channels recorded data collection to to ascertain a the data file. integrity recorded waveforms. A utility to related allow plotting the on same display multiple graphs of related or non- information. A utility to frequency allow band the operator widths based to alter various search and analysis parameters and upon specific dataset characteristics. 4 DISCUSSION 65 The capability to obtain a printer Useful dataset cation. hard copy of during statistics obtained graph any displayed in the the processing appli included in the are display. Within the data and time are acquisition procedure, the 'stamped' automatically as a comment at A file utility to enter, examine, entry This application for cedures analysis originally designed been important to of notations made which blood with this the time of the date, recording. the data files enables each studied subject. expansion in pressure to include future processing expansion pressure waveforms. include blood channels, file name, and alter comments within has the capability for of number of mind. The data In fact, acquisition procedure was recordings many pro have already information. Software Limitations & Operational Notes 4.1.5 The method employed rate dataset of these data quent are removed disruption data removes in still points of the heart remains. rate data would not evaluated for the instantaneous heart divisor should represent non-linear amount (1/4095 has been not points interpolation the the being series number of points tion 2.4.1 During in the instantaneous heart constructed of of but rate the median would resolved as of 1/4096), this date. filter effectively mentioned alter to produce points their the in Sec value as {HRV. Values}, the intervals in the target array a subse dataset. {IHR.Array} number of to for the detected, but originally (4096). The difference in the resulting as opposed removal variability dataset. It is true that few Implementation remove points from the {Peak. Indexes} dataset. The to the comparison number of points spurious disrupts the time-event points development for correcting difference of values 0.025 (4095), differ percent. by This not the a small situation DISCUSSION 4 During the was 66 window was Hanning amplitude window of expressed is exactly in the This Clinical Brain Injury. For many years, in blood pressure, cardiac output, body, including the while certain was a density, not been quasi-steady states (as would also well as is stimulated by state with are In the literature, ity are frequency by high-frequency brain injured and 29 A the nervous has sympathetic Hz) is window of a rectangular the signal, as was not a valid injury heart change exist the with an in baseline heart rate, many systems of a state of chaos most increasing study rate in autonomic cardio instead behaviour regularity reported variability, chaotic the herein has even when and non- revealed the body cardiovascular one in which the heart and parasympathetic rate current variability are study, there low-frequency nervous solely systems. mediated was a moderate power neural pathways perceives as are High- by the decrease between the severely (Table 1). This implies that both the body rate variabil low-frequency fluctuations (0.04-0.15 Hz) decrease in patients analysis of that in heart In the system. brain dead noxious stimulus thought to aging) illustrate revealed and a significant and parasympathetic it this date. Recently, information derived from the fluctuations (0.15-1.0 parasympathetic in spectral mediated since noxious stimulus29. via non-invasive methods jointly by power of held that the little associated associated with almost no strong Hanning a be halved. This resolved as of variability in these behaviours [13]. The brain that brain death is by that the and vascular resistance. system, originally done was same signal multiplied assumed Values}, Result Interpretation [13]. As such, health is disease the medical practitioners cardiovascular state This two. of then Laboratory and to the Blackman filtered {HRV. area of a signal multiplied It has vascular system existed steady factor a power spectral situation window one-half as amplitude. unity statement. one of by multiplied determined that the total unity 4.2 the application of sympathetic irrevocably damaged between potentially tissue damaging. 4 DISCUSSION severe brain Several the 67 injury and brain death. cold pressor test test is designed to the and to blood pressure of beats per minute occurs blood 24 increase in 7 mmHg for the adults by serum an average of In the brain cardiovascular injury 27 frequency heart but these changes were not These of subjects). fluctuations pathways results other of elevated period brain dead linear-type An The due to are cold pressor a constriction An increase in stimulus. increase in the heart [29]. Serum of which rate of 10 2 from catecholamines which normal values of 447 pg/ml, respectively [37]. During levels increase in normal norepinephrine 139 pg/ml, respectively [29]. was no measurable response in during patients with significant that there is severe Small testing. cold pressor were evident 6) a (most injury in autonomic absolute changes in low- Glascow Coma Scale < likely due disruption brain of the to the 6, small number efferent and complete occurred norepinephrine but near undetectable in the brain dead catecholamines patients. measure of and epinephrine within 24 hours sympathetic interruption of of brain levels of subset of their these same injury, cate three brain dead injury, however, levels after similar of plasma catecholamines severity in the brain injured. With of severe in the severely brain near undetectable This indicates that the level varying levels A patients. levels dropped to catecholamine catecholamines with determined to imply cholamines were characteristic 24-48 hour and studied, there injured (Glascow Coma Scale < had pg/ml and two in brain death. Elevated levels patients 71 statistically neural pathways cardiovascular these rate a pg/ml and response the testing laboratory for by epinephrine pressure region of average normal adult population activity in blood concomitant with an samples are analyzed testing, pressor arterial heat in the conserve epinephrine and norepinephrine were cold dysfunction, of autonomic measurement of plasma catecholamines. stimulate an of cutaneous vasculature collected for the detection methods exist is a to not a precise measurement of plasma a non-linear correlation may be with additional studies. aim of the current study was to seek a correlation between heart rate variabil- 4 DISCUSSION ity spectral power No direct serum jury. (linear) levels the levels and the decreases steadily results catecholamines during brain (epinephrine increase death. This is in From the information of variations in documenting with existing of corroborative brain during injury severe levels increase brain Woolf during heart injury [37] but of the brain injury. variability rate drop brain in power variability to brain death. near zero that in who reported severe levels humans, brain injury. methods non-invasive power and severe during immediately following in the behaviour developed autonomic cardiovascular system brain death. This technique definitively severe and are near zero in this study, the tests to rate norepinephrine) low-frequency agreement with obtained for the detection useful and indicate that total epinephrine and norepinephrine may be determined between heart the severity with during of plasma catecholamines correlation was of catecholamines However, Plasma 68 establish could be in used conjunction brain death in humans. Further studies seem warranted. Septic Shock. creases following levels. cholamine cert with arterial The sepsis rabbit endotoxin-induced blood pressure during levels is not sufficient the system is primarily plasma catecholamine pathetic is levels and activity is inhibited suggested that inhibition sepsis may research involving provide more identify decreased the the by blood power Thus the shock. cate decreased in con sole onset of septic shock low-frequency neural power onset of septic shock. activity by de increase in a concurrent variability pressure in monitoring of Since rabbits. activity, depressed may indicate that sym From this conclusion, it endotoxin contributes, at of endotoxin shock. the insight arterial sympathetic of sympathetic efferent least in part, to the development Further to rate endotoxin regulated during mean septic shock without However, low-frequency heart catecholamine endocrine study indicated changes on specific in autonomic mechanisms cardiovascular activity of sympathetic neural during inhibition. 5 CONCLUSION AND RECOMMENDATIONS Conclusion 5 This software application function cardiovascular pressure analysis states should be Relationship improved derstanding would sults the of by pursued. non-invasive means. these term work of a internment) iological be characterization of autonomic development into blood program of other physiological conditions and disease Brain Recovering brain power region injury compared (0.01-0.15 patients. spectrum of follow-up Injury more complete un the heart examinations to the tend to indicate Hz) A previous of Patient. rate these data variability patient. collected Re (during for further investigation. Cardiac Feedback-Control Model. may contribute teractions between the findings from out-patient would Further low-frequency in the in the follow. of pediatric changes examinations patient's original This reasons levels in the for recovery long Development investigations Several be facilitated through of a significant asset Spectral Power to the power chances Recommendations has been and clinical of Increasing and 69 to the development cardiovascular additional studies of abnormalities may be a autonomic and heart rate forthright of a feedback-control nervous variability using endeavor in systems. model of Integration in of subjects with various phys developing these feedback-control models. Future Investigation into Arterial Blood Pressure Variations. Research to employ pressure waveforms inclusion of blood ration signals will spectral analysis is currently underway pressure information facilitate further at methods to investigate the Rochester Institute during the variations of Technology. The original acquisition of studies of pediatric brain injury in blood EKG patients. and respi The study 5 CONCLUSION AND RECOMMENDATIONS of correlations between heart variations open avenues of may rate variability, 70 catecholamines understanding into the levels, mechanisms and blood regulating pressure cardiovas cular activity. Potential Applications. Efforts to develop non-invasive means real-time is being portable analysis may processing of considered at prove very useful the EKG to units which evaluate for extract this time. This clinical use. As rate mentioned spectral content of would provide heart variability in Section 1.4.3, the derived HRV bedside data by signal on cardiac autonomic efferent activity. There propriate from are also potential treatment exposure therefore be autonomic to able applications of wounded personnel. certain to military assist disruptions. chemicals or for immediate field diagnosis Corruption biologic toxins. in identification of autonomic control A and subsequent portable treatment analysis and may ap result unit may for such protocols REFERENCES 71 References [1] Akselrod, S., D. Gordon, R.J. COHEN. Power of beat-to-beat spectral analysis of D. Gordon, J.B. R.J. COHEN. Hemodynamic 4m. J. Physiol. S. SHR: investigation [4] Baselli, G., M. ELIASH, by S. Cerutti, AND quantitative approach [5] Baselli, G., MALLIANI, arterial AND blood as fluctuation: A.C. Barger, and a quantitative probe Science 213:220-222, 1981. N.C. D.C. Snidman, investigation regulation: AND by Shannon, spectral S. COHEN. Hemodynamic i4m. J. Physiol. Civardi, G. RlZZO. Heart analysis. D. to diagnosis in 253:H176-H183, Lombardi, rate regulation variability A. 1987. Malliani, signal in M. processing: cardiovascular pathologies. a Int. J. 1987. Cerutti, S. Civardi, M. PAGANI. Spectral pressure Shannon, rate Madwed, Oz, S. an aid 20:51-70, S. heart spectral analysis. PAGANI, Bio-Med. Comp. O. D.C. 1985. 249:H867-H875, [3] AKSELROD, S., MERRI, Ubel, cardiovascular control. [2] Akselrod, S., AND F.A. variability F. Liberati, D. Lombardi, and cross-spectral analysis of signals. Computers and heart Biomed. Res. A. rate and 19:520-534, 1986. [6] Berger, R.D., algorithm for S. Akselrod, spectral analysis of D. Gordon, heart and rate variability. R.J. Cohen. An efficient IEEE Trans. Biomed. Eng. BME 33:900-904, 1986. [7] BERNE, R.M., St.Louis, AND rate Physiology, 2nd ed., C. V. Mosby Company, 1988. [8] BREBOROWICZ, G., heart M.N. LEVY. variability J. by MOCZKO, J. spectral analysis GaDZINOWSKI. Quantification in growth-retarded of the fetal fetuses. Gynecol, obstet. REFERENCES 72 Invest. 25:186-191, 1988. [9] CHESS, G.F., inputs R.M.K. Tam, on rhythmic variations AND F.R. CALARESU. Influence heart of period in the cat. of cardiac Am. J. Physiol. neural 228:775- 1975. 780, H. [10] Cowan, M.J., Power R. Kogan, spectral analysis of heart Burr, rate S. Hendershot, variability after and L. Buchanan. biofeedback training (draft). J. Electrocardiol. 1975 (summer). V.K.-H. [11] CRAELIUS, W., ysis of arterial blood CHEN, M. RESTIVO, N. EL-SHERIF. Rhythm AND anal IEEE Trans. Biomed. Eng. BME 33:1166-1172, pressure. 1986. [12] FlNLEY, children. J. P., S.T. Spectral NUGENT, analysis of AND W. HELLENBRAND. Heart-rate variability in developmental between 5 changes and 24 years. Can. J. Physiol. Pharmacol. 65:2048-2052, 1987. [13] GOLDBERGER, A.L. AND B.J. WEST. Fractals in physiology and medicine. Yale J. Boil. Med. 60:421-435, 1987. [14] Goldstein, B., D. WOOLF. Assessment atric brain injury, [15] Goldstein, B., (abstract) [16] Goldstein, B., KELLY in M.H. Pediatr. Res. by heart rate spectral analysis in AND brain in October, 1991, P.D. WOOLF. The injury and P.D. pedi 29:28A, 1991. brain death, severe brain injury and and brain pp 28-29. D.E. DeKing, D. DeLong, M. 1991. and Kempski, D.J. DeLong, D.E. DeKing, C. Cox, Am. Acad. Pediatr. following Colloq., function rate power spectrum changes D.D. NICHOLS children Care of autonomic (abstract) P.D. WOOLF. Heart death, DeLong, M. Kempski, D. DeKing, C. Cox, Kempski, C. Cox, M.M. autonomic cardiovascular state (abstract) Proc. Pediatr. Crit. REFERENCES 73 [17] Goldstein, ski, P.D. dotoxin D.R. WOOLF, shock Kempski, R.B. N. LUND. Heart AND in the rabbit, D.R. [18] Goldstein, B., R. deAsla, D.E. Stair, (abstract) N. Tipton, Lund, and plasma catecholamine changes Clinical [19] Res., 40:297a; The fundamentals of [20] Inoue, K., S. Proc. Pediatr. Crit. Care DeKing, during endotoxin shock en 1991. Colloq., D.J. P.D. Woolf. Heart and during DeLong, M.H. rate power spectrum in the rabbit, (abstract) 1992. signal analysis. M. Miyake, spectral analysis of DeLong, M. Kemp rate power spectral changes R. deAlsa, D.E. Stair, D. DeKing, heart AN-243, Hewlett-Packard Company, H. Kumashiro, rate Ogata, variability in traumatic and 1985. O. Yoshimura. Power quadriplegic humans. Am. J. Physiol. 258:H1722-H1726, 1990. M. [21] Japundzic, N., of analysis blood Grichois, pressure and P. Zitoun, D. Laude, heart rate in conscious and rats: J. Elghozi. Spectral effects of autonomic blockers. J. Autonom. Nerv. Sys. 30:91-100, 1990. [22] KlTNEY, R.I., Oxford UK:, tral [24] MILLER, ing, F.B. Evaluation analysis. Press, EDS. The study of heart-rate variability, 1980. Axelrod, S. Akselrod, D.W. Carley, of autonomic and dysfunction in familial dysautonomia CD. Shan by power spec J. Autonom. Nerv. Sys. 21:51-58, 1987. B.F. and allied AND C.B. KEANE. Encyclopedia health. Philadelphia, W.B. [25] Moody, G.B., respiratory O. ROMPELMAN, Clarendon [23] Maayan, C, non. AND R.G. signals from Saunders, Mark, A. Zoccola, multi-lead and EKGs. IEEE and dictionary of medicine, nurs 1987. S. Mantero. Derivation 21:113-116, 1985. of REFERENCES 74 [26] Pagani, M., Pizzinelli, F. G. S. Lombardi, Sandrone, G. heart interaction in K.M. analysis. i4m. J. Physiol. [29] Robertson, D., AND G.A. in [30] Press, W.H., B.P. Cambridge of autonomic M.A. 21:499-502, Caudill, I. function in humans 248:H151-H153, spectral analysis sympatho- vagal 1985. Kutz, by D. R.J. Adam, Cohen, heart D. and rate spectral 1985. stimuli that release neuronal and adrenomedullary Circulation 59:637-643, 1979. Flannery, S.A. Teukolsky, art of scientific University Press, [31] Shannon, D.C, M. Johnson, R.M. Robertson, A.S. Nies, D.G. Shand, man. Numerical Recipes. The rate. Macaulay, J.A. OATES. Comparative catecholamines Piccaluga, of electrical axis variation Kilborn, A.C Barger, D.C. Shannon, H. BENSON. Assessment P. dog. Circ. Res. 59:178-193, 1986. respiratory information. IEEE R.J.B. [28] Pomeranz, B., Gordon, A. Malliani. Power and R. ROSSI AND L. VERGANI Detection extraction of E. Dell'Orto, Furlan, R. Rimoldi, pressure variabilities as a marker of man and conscious [27] PlNCIROLI, F., for the blood rate and arterial S. Malfatto, Turiel, G. Baselli, S. Cerutti, of O. Guzzetti, D.W. computing. and W.T. Vettering. (FORTRAN version) New York: 1989. Carley, and H. Benson. Aging of modulation of heart Am. J. Physiol. 253:H874-H877, 1987. [32] SHIN, S-J. W.N. tonomic TAPP, S.S REISIMAN, regulation of heart IEEE Trans. Bio. Eng. [33] Siimes, A.S.I., METSALA, L.T. rate AND variability by B.II. NATELSON. Assessment the method of complex of au demodulation. 36:274-283,1989. I.A.T. Valimaki, K.J. Antila, M.K.A. Julkunen, T.H. HALKOLA, AND H.S.S. SARAJAS. Regulation of heart rate varia- REFERENCES tion by 75 the autonomic nervous system in neonatel lambs. Pediatr. Res. 27:383-391, 1990. [34] VAN of VOLLENHOVEN, E., A.J.M. BART, blood Kitney pressure. O. and [35] WEISE, F., a spectral analysis. K. on heart rate Nerv. Sys. AND genesis of BALTRUSCH, 26:223-230, R.W. in assessing AND during cardiovascular UK: Clarendon Press, U. RUNGE. Contributions heart rate J. Autonom. Nerv. Sys. fluctuations [37] WOOLF, P.D., cholamines to the Oxford, eds. HEYDENREICH, vagal mechanisms [36] WEISE, F., E.F.A. DEPRETTERE. Measurement In The beat-by-beat investigation of Rompleman, F. AND fluctuations 21:127-134, load: 1987. of sympathetic and during orthostatic load: 1987. F. HEYDENREICH. Effect orthostatic function. R. I. of low-dose a spectral analysis. atropine J. Autonom. 1989. HAMMIL, outcome L.A. Lee, ET AL. The predictive value of cate in traumatic brain injury. J. Neurosurg. 66:875-82, 1987. [38] ZlEMER, R.E., tinuous and W.H. Discrete, TRANTER, AND D.R. FANNIN. Signals 2nd ed., New York: Macmillan and Systems: Con Pubhshing Company, 1989. Appendix A Signal The processing separate of signals entails nents. Signal with a summing junction circuit, involves many steps, types appendix include Ziemer [38], Continuous-time their domain. of analog A. 1.1 Any composite Hewlett-Packard Analog these two signal will involved signals are in time. as multiple mono- frequency of spectral that from and verbal this are also discussions tech identification, a several published with few different which sources engineering faculty. Signals every signals which possess a value of Obviously then, a continuous-time signals spectral content. possess a unique value at For the compo constitutive complex modulation employing described below. There [19], those into their extract from construction of a signal component30 purposes Analog characteristics. imply adding work extracted signals are signals a selected point both a as signals be handled uniquely to Continuous-Time A.l for is simply some of which are of signals which must This or as for the decomposition, general operations: of complex construction can occur as Signal niques. two decomposition and sources, Fundamentals Processing a continuous-time remainder of analog this point of infinite analog discussion, time in resolution signal possesses reference to an signal. The Fourier Series signal summation or waveform of weighted of a periodic sinusoids. nature This can summation Fourier series representation of a periodic waveform. Fourier series 30Spectral representing components some consist of waveform, x(t), the be amplitude component. 76 and represented is more by an infinite commonly known Equation A-l shows a series as trigonometric in the time domain. The Fourier phase shift for each the contributing series frequency APPENDIX A 77 coefficients31, an bn and mean value of x(t ) over be must for evaluated the time domain. A fundamental PC x(t ) = a0 + series complex exponential is 2J form, nwo' + x(t) = other A0 5Z ^n ways, Equations A-2 shown as is denoted to the as u>o. (A-l) sin nu>u n=l in two expressed frequency evaluates ex a" cos n=l The Fourier The a0 term each x(t). An + a cosine and cos{nu0t A-3, + trigonometric form and a respectively. (A-2) 6n) n=l oo XneT""* (A-3) x(t)= oo n= The coefficients obtained are cients for the indirectly from for the the Euler A Sample Case. An the represents a real cosine a new function after = yi(0 + lfe(0 + 3/3(0 Y(t) = 5cos(2a;0f + function. coeffi series coefficients 07r) component + the (A-4) series shortly. signal, Y(t). Y(t) 31The Fourier 6n, directly from dt x{t)e-^^ introduced combining three different frequencies to form tion A-5 are obtained and The for Equation A-l. A-3), Xn, using the Fourier example of process of I T0 Jt0 = concepts of spectral components form, used A-2), A0, A, a single step. Xn tion coefficients form (Equation complex exponential Equation A-4 in the trigonometric form (Equation cosine is shown Equation A-5 signals {yi(t), below to illustrate illustrates, in yi{t), It important here to and note by y3(t)) of that Equa summation. 3cos(8u;uf-7r/6) + lcos(16u;uf + tt/3) are obtained equa an integration of the product of x(t) (A-5) and a sine or APPENDIX A The 78 Figures A-l by components are for signal. content, of x(t). multiples or Band-limited The harmonics say in the Fourier are needed and complex exponential obtaining the frequency of, maximum signal summed dif of signals of these Analog Signals of trigonometric directly spectral integer component the composite, shows illustrated A-5, is in Equation the three which shows Figure A-2 phase. signal given in the time domain. cosine convenient the and simple Figure A-l Spectral Content Both the or A-2. and fering frequency A. 1.2 the construction process of Mu>u, series. signals have of frequencies component of the fundamental frequency very important signal place u)u. finite in signal possesses a number of a are which na>0, If x(t) x(t) is termed series component, are expressed as a maximum and If this occurs, the the Fourier frequency amplitude and phase of each then only a forms terms (M) band-limited and will processing be mentioned again. Since there is to use two plots an amplitude and phase if graphical component amplitude versus component phase versus series, cosine two-sided either frequency form of representation frequency frequency trigonometric for or spectra, the DC of the is termed is termed complex spectra are used each component coefficients an amplitude is desired. spectrum, component display the (frequency The and The form a phase spectrum. exponential, determines to the it is necessary frequency, of whether plot the plot of the Fourier one-sided spectral components of x(t of zero) of or ). For always possesses a phase value of zero. The One-Sided Spectrum. The be frequency plotted frequency in value. to form spectrum a one-sided is shown coefficients of Equation spectrum of x(t). in Figure A-3. Note that all A-2, Au, An, An and 8n, can example of a one-sided frequencies are non-negative 79 APPENDIX A !<> -4. = 3 o*a <1 t 3 eoi < t > ? ! wl< m> <M> 1 0*> !> <llt * > - ^/VWW\AA/WVWW TSii- 7735 Figure A-l: Example of three mono-frequency analog = <t> .ilV l<t> ^* t Figure A-2: Example ? !<> rs^5 ? signals. 3<t> 'M5 r^( lno.ili) of summed (composite) signal. APPENDIX A 80 Amplitude 0 2u>0 4ujo 6u>o 8u>0 lOa^o 12^ 14u;u 16u>u 18u;,j 20^ Frequency (radians/sec) + 7T/2 + 7T/3 + 7T/6 Phase (radians) 0 2u>o 4u;0 6luu 8u;0 lOwu 12u;0 14u>u 16u>tj 18u>u 20^ -tt/6 -tt/3 -tt/2 Frequency (radians/sec) Figure A-3: The one-sided frequency spectrum of the example composite waveform. APPENDIX A 81 6 Amplitude 5 4 3 t> ( > 2 i> < t 1 T T -16u;(i -12u;0 -80/0 4w0 -4u/0 80*0 12u;0 16u\, (radians Frequency /sec) + 7T/2 Phase + 7T/3 (radians) + 7T/6 16u;0 -120^ -80)0 0 -4u>0 80^ 4o>u , -tt/6 12o>u 16u;(, Frequency (radians/sec) -tt/3 tt/2 Figure A-4: Note that The two-sided amplitude spectra one-sided spectrum. The frequency is an even phase spectra spectrum function is an odd of the example composite with amplitudes one-half function. waveform. those for the APPENDIX A 82 The Two-Sided Spectrum. The that for any specific signal component of may exist as indicated (k<0) negative have 5u0) trum has 'negative' the on shown above portion is the as Although exist. is representation phase for the is an information frequency frequencies right. in the useful frequencies (i.e. representation on left, the A- 7 a is the DC about odd a Ot the of be dis can in Figure A-4. This two-sided the center, component at complex exponential frequency of portion in the is the Ou^ (DC), function. Note that the coefficients form33 spec 'positive' and of the function phase. the It (-e-jUA , spectrum. (-ej0v) + + _eWe) conjugates3^ A'0, denned ej(~ute^ = even function and large ejW (*e-i*/e\ ( Lj*/3\ QeW3) + -e-J"/A and are complex Except for frequency, Jfcw0, is an e-j2^1 For Two-sided to One-sided Spectrum Conversion. sided is graphically in seen amplitude coefficients are one-half as g-JlGWu* ( _|_ for Equation A-3 be amplitude c-;*;0t cients can \ one-sided spectrum. + 33Euler's theorem, coefficients in Equation A-5. For the A"_2 term (first term shown), \e~^ , the Y{t)= '""The A*. This implies that negative in the Xn contained spectrum as shown Equation amplitude and Figure A-4 that the some amplitude and phase complex coefficient frequencies meaning, the and phase two-sided a frequencies Y(t) no physical the presence of (k>0) and positive magnitude in played the frequency32, ku0, A-3) illustrates frequencies. complex The by form (Equation complex exponential by the all complex-valued k for f\ (coswt -oo < k < jsinut), is form A' a jeuut (A.6) eJlGUut , real signals, the perfectly Xn symmetric coefficients can be coeffi double- related the oo. used to relate trigonometric functions to com plex exponentials. 34Complex the complex only the vectors conjugates are represented as phasors or a pair of 5-plane. Added together, the imaginary rotating in opposite directions in vector components cancel each other which real components with a combined magnitude of 2|X|. leaves APPENDIX A A and 8n 83 coefficients An = from Equation A-2 2\Xn\ by the following relationships: Tm Xn 0 arg(A'n) = (A-7) arctan Re An and, Au |A'u| [ = x(t)dt (A-8) . Discrete Signals A. 2 A transformation discrete now = of waveforms though, a the Fourier to describe discussion of series will result in a form of a for use with For is discussed in Section A. 2.1. spectral content and the definition more appropriate discrete waveform is in order. X(l) f ' 0 (a) T IT Analog signal .r(K ' /T>. - x^nAi) >-f r= .i/ S Samples n = 0. I. (b) Sampled Figure A-5: Representation An analog, continuous-time time signal, x,(n), to be this process: by at a uniform - I version of a a \ . signal, x(t), processed sampling x(t) va/ = discretely must digital rate, be sampled converted computer. and analog into Two a signal. digitized, steps are then quantizing the discrete- involved with signal value at the APPENDIX A 84 sampling instant to result is termed digital By analog-to- sampling the time At of some 1/ fs = N using =* a The is illustrated signal values for each sample. frequency, fa (in hertz), by Equation (n the signal value have sampled values {x(nAt)}, = conversion of digitized fixed sampling sampled points. x,{n) The value. conversion and yields a seconds which x{t) = A-9 a constant and shown 0,1,2,..., N x(t) can spacing in in Figure A-5. (A-9) 1) - be Discrete Fourier Transform A. 2.1 In Section A. 1.1, plication of required the exponential Spectral continuous then only analysis continuous of a just series. over finite However, number of terms number of convenience. of terms unless is, discrete waveforms can as continuous waveforms can form exponential Note that the 27r/0* of and through ap Xn coefficients constraints. x(t) was Sec found to be were necessary. That signals the integration is developed in This development for discrete from the evaluation of waveforms is be a be manner represented as a sum of represented called to that similar by a sum of continuous the discrete Fourier transform. The discrete Fourier transform is derived Discrete Fourier Transform Derivation. directly the its domain because infinite was available analog signal, x(t), discrete waveforms. sinusoids sinusoids. Fourier summation required an band-limited, discrete spectral content of some x(t) to be ondly, the for discrete digital a original signal by approximated in the Fourier series, which k terms have been is reproduced substituted35 for here for wut and n, respectively. oo Xkei2kKfot (A-10) x(t)= h= oo where, Xk 35r 5The circular expressed in frequency, u)0, is ^ = related radians per second and f0 is f dt (A-ll) . 1 JT to the frequency term, /0, by expressed in cycles (points) w0 = 2nf0. per second. The term u> is APPENDIX A 85 Transformation substitution x(t), results tuted into /,j, and appears of the Fourier series into the terms into the of approximated in the sequence, a:s(7iAi),for n Equation A-ll for T/N for dt. The resulting as a summation over X* = The x(t). i N-l 7F E ^ In regard frequency to the and = *n = {A'jt} represents the , the argument of Recall that The DFT is in the replaced by represents sequence include: = 0, 1, ..., nAt is signal substi for t, 1/T for reduced N-l. and (A-12) series term, the development of are A-10), e~j2Kkht, the = = represents form in the xn (A-13) (A-14) 0,l,...,iV-l) generally of {x}, frequency fc/u DFT, /0 1/T, Xk in value frequency /0. In is determined from the represents = results Each complex. the fundamental this where equations xu,x\,...,xk.\. = x,(nAt) JV-point time series, of a harmonic (Equation xn the inverse 0,1,..., N-l) = (n which of a specific and in the time domain. xn ^ E A>'(2^"\ values Equation A-13 xn, Equation A-13 (k The DFT as series: S*"e-i(2,r/")B*. exponential the iV-point time used x(t) signal, the DFT. Fourier during 1. This Equation A-14. These two as for the iV-point time contribution the for k defined now is defined (IDFT) dataset containing N exponential term of - the of as: x,(nAt)e-i2imk,N Equation A-14 Xk Periodic Nature the pair original domain iV integral is algebraically approximated N terms ..., requires n=0 discrete Fourier transform Fourier transform 0, 1, 2, = Discretization equation. other substitutions The discrete Fourier transform (DFT)is a Xk discrete Fourier transform the where klh T harmonic was the of /y. period of series xn. periodic in iV-points because summation which forms x(t). of the periodic nature of the e-^2v/N^nk APPENDIX A 86 Proof: By letting the new k k+N = expression and substituting into the to the evaluates same complex value exponential, the as original Given: expression. e-j(2*/N)n(k+N) e-j{2K/N)nk-j(2v/N)nN _ e-H?*IN)nke-Ji2*IN)nN = but e-j(2rr/N)nN g-j(2rnr) _ j _ thus the fact that -j(2*/N)n(k+N) the DFT is proves The periodic nature of the in reconstructed illustrates this time a xn phenomena The frequencies {X,,} dataset is N could be 'shifted' by, say, and still remain periodic spectrum of a will be in by {X} size and (y - some l) is in time range to one extra frequency the from, coefficients Since N points in TV points, T. Figure A-6 period signal. l)/0 [hertz]. Since frequency (-y + lj /0 to (yj f0 asymmetric36 an to periodic in those N points, this range two-sided the range [hertz], frequency signal. Recall from Section A. 1.2 concerning analog 36There is the DFT is with {X} signal x(t). from 0/o-(iV in N. This is effectively band-limited using the arbitrary transient periodic points k. analog and since periodic all when original T seconds, clearly for represented points iV-points, for the replaces period of signal in e-j(2*/N)nk the DFT is important Recall that xn reconstruct xn. were obtained periodic _ element which is: y/o- signals that a two-sided spectrum can APPENDIX A 87 Actual a) b) Time c) Figure A-6: The by the DFT be converted done for the discrete into to N. To and of digital compares the just obtained DFT, on if the The the y/0 resulting from the assumptions made number order of must operations This increased be equal computational number of values and for TV [38, to can speed series an a power of enormous 2k for integer k and values of speed, requires the FFT > The an only faster than the DFT not come without restriction. = of additions for large computational operate much two (i.e. TV form spectrum and developed. The FFT differences between the DFT p458]. multiplications therefore increase therefore frequency be signal. become was can also an equivalent a one-sided analog can (FFT) does by invoking of complex TV2, and This original signal was real. term. Thus for as the fast Fourier transform TVlog2TV TV, be number of operations computer. points, Assumed input record discrete time of a the DFT. of the }) A-8 but omitting the compute a algorithm called a ({A signal can reduce an order of a one-sid^d spectrum spectrum Computation required record algorithm. Equations A-7 of a the time periodic nature of input on number 0). Table A-l algorithms for a APPENDIX A 88 Table A-l: Comparison of Number of A. 2. 2 Three They methods are are detailed FFT 2 4 48 16 3 16 960 128 8 64 16,128 768 21 256 261,120 4,096 64 1024 4,190,208 20,480 205 2048 16,769,024 45,056 372 4096 67,092,480 98,304 683 of by extraction of spectral transform, The in itself in information auto-correlation p463] but uses a correlation can [38, The The method time [38, analysis, p463]. used method system a can yield a graph section. signals. The other below. technique that involves multiplying the cross-correlation method for is discrete and cross-correlation following briefly described of signal to indicate reveals periodic by a time-shifted similarities (repeated p463]. two different signals; be are auto-correlation units of Cross-correlation. but [38, FFT. Discrete Signals described for Ziemer and Speed Factor 4 itself. The resulting dataset version of function DFT 8 elements within a signal. nique Real Multiplications for the DFT The discrete Fourier transform is detailed in the Auto-correlation. trends) of 2 the discrete Fourier are Number Points Spectral Content analysis. two the one is most identification is similar likely to the autocorrelation tech used as a reference signal. by determining the system's Cross- transfer APPENDIX A A.3 The to Considerations process certain loss, and various that types or corruption, are relevant sampled information, in the greater enough. selection of of frequency. band-limited to The DFT sided the resolution. spectrum record. the total is apparent The Nyquist a that there bandwidth if there are section will if occur the sampling are: number of points discuss only those discrete Fourier transform at frequency of ranging in of the frequency must be a rate or all some produce that frequency the signal original accurate component points in that in the information is sampled, frequency (/at) of a signal signal. the /, must is equal Sampling cycle of each Sampling theorem, signal at compo must be /s/2. information for the development frequency from DC (0/,) spectrum the length of or closely spectrum which trade-off between to /s/2. is dependent the time DFT points, usually limitations in the to similar becomes very important. The Sam possess least two frequency Increasing appear if the DFT is to at which frequency rate yields number of 'wider' gives to series This is important in resolving low Increasing quency, rate. rate words, to satisfy the a maximum time sampled other frequency line) of a This will However, can provide accurate spectral frequency ('width' In these of results of an applied frequency the largest faster than the Nyquist nent Some duration (thus the record the sampling signal, the original frequency information may of spectral process. The time-series, xn, rapidly than the Nyquist to twice the or masking attention requires xn. pling theorem dictates that for the time contained discrete dataset a as well as others. to affecting the Theorem. Sampling signal, x(t), if be yield the sampling 'noise', of to the time-series spectral to signal analog during exist the Discretization Process of in the discretization process, total sampled), concepts a sampling conditions rate used (DFT) of things certain The 89 record spaced upon by increasing frequency volume of available of frequency components. the sampling fre higher frequencies. resolution data resolution the length increases the frequency encompasses The of a one storage. and It frequency High sampling APPENDIX A rates for A. 3.1 90 long durations in enormous data storage requirements Spectral Abberations AIiasinS- The reason a phenomena called frequency These can result behind If aliasing. components greater falsely translated application of the a signal than fs/2 frequency components and will corrupt is Sampling sampled slower will be 'folded frequency c) Figure A- 7: The effect in the time domain into the themselves content of a) elimination of than the Nyquist rate, those over' components will alias the original theorem is the the original passband. as lower frequency signal. Actual input Assumed input of a non-integer number of cycles in a sinusoid signal. Spectral Leakage. of cycles for all of its A component does occur, due to the resulting frequency sampled may [19]. This caused by not necessarily frequencies due to the finite periodic nature of amplitude results components signal the effect the sharp DFT, as in the an leakage integer number length. When this record a smearing-out is known peak possess of and the energy in the is due to the high 'replicated' signal, as the DFT APPENDIX A sees it, in the as 91 input assumed to abasing in Figure A-7. shown which Leakage can criteria. Figure A-8-a cycles and occur Thus, leakage signal. results even in masking with shows Figure A-8-b These sharp a a shows peaks contain can give lines frequency false frequency that signal information similar components. meets the Nyquist sine wave with a non-integer number of mono-frequency affect spectral of actual properly band-limited the high frequency harmonics leakage creates during spectral analysis. iltemLtime function J? ^ftfTEMMTE ffnftlE! ) 3l1 PFJ rvpdt* h*> n^wiivt* MFTER Fl \M>V* *CT p^rwJ< I" t"*1* W-W O FY~T Figure A-8: Leakage 'windowing' effect of recorded for simply from the noise in the minimize Random Signal Noise. being effects to and analysis. For example, data upon the collected nt*4f!; iMth a frequency domain environmental process during a 12-bit are noise of noise funcrrct mono-frequency sinusoid a is introduced into the digital levels resolution introduced into often analog to digital number of quantization using of a -4<>%ic+ and it. An inherent level quantization is dependent (vntr'u gives conversion. applied 4096 to the The signal potential incoming quantization signal signal. levels. The APPENDIX A 92 quantization noise level is in decibels from: computed Quantization Noise A.3.2 Reducing Aliasing. Two 1. Sampling 2. Filtering the -20 log 4096 = dB -72.2 (A-15) . Spectral Abberations. may be precautions which the = to to reduce aliasing faster than twice the Nyquist signal at or signal used eliminate or minimize rate frequency are: for that signal; or components greater than fs/2- Filtering can be dataset. Filters Leakage. 1. to sampling the analog performed prior will be discussed the width of the DFT (i.e. increase 2. Application the high of a the data reduce spectral by increasing window the leakage which are: number points used in duration); record effects of to employed window, to taper the frequency the discrete shortly. Two techniques may be Increasing signal or afterward on ends of the sharp peaks the sampled signal in the assumed to zero, input signal will reduce (described previously). Figure A-9 peaks' by that shows effect were evident a smooth Many the of windowing in the time domain. in Figure A-8 transition imparted window is derived from types a cosine can be by a used function and when and application of a window to may actually introduce the signal is duplicated in time, 'sharp are replaced windowing function. but is a common shown 1 / The the Notice that the a signal type is the here for TV Hanning window which points: 2(n + 0.5)7r\ to effects of reduce leakage leakage for total signal power components that do have will reduce frequency APPENDIX A 93 j a) Actual input b) Assumed input Window function c) dl Windowed input Figure A-9: The an integer a window as it number of cycles function to could be if there a Signal Noise. tion he of a were an performed prior Any filter no smaller signal. to intrinsic Figure A-8-c leakage. integer As shows The the spectral number of cycles in the affect 'line' of application is sinusoid not as mentioned above narrow but the is primarily accomplished for abasing reduction, this or afterward on the discrete time by to the sampling 'line' applica filtering series from Equation levels). The process and is reason A- 15 (after substituting for for this is that this unremovable. can dataset. reduce quantization noise should possess a stopband cutoff value obtained of is clearly discernable. of noise contamination actual number of quantization is windowing in the time domain. reduce to data sampling employed that the to frequency Reduction filter to the sampled. signal representing the dominant effect of level '4096' the quantization noise APPENDIX A Signal 94 Filtering Techniques. analog filters and Digital filters data after A. 4 for anti-aliasing used of frequency in Section 2.4.2 algorithm. one value filters used for signal processing: are used with continuous-time analog discrete time series. a signal to series after produce a the discretization process. Use before and (HRV) de and reduction of noise contamination for each point Determination Density in the heart components processing this entails The FFT processing signal analysis results in a is determination of the dataset. The conversion process power spectral frequencies in the density analyzed is signal, not by to signal fast Fourier transform or array of complex However, points). processed in the HRV obtain the power the 'power' units, but numbers; rather as a [30, in To this end, a power spectral contained (FFT) end purpose signal. Equation 12.7.5 in Press expresses in a variability discrete dataset spectral power outlined dataset rate by signal in the HRV dataset (4096 the Fourier transformed dataset is further The of collection. The detection this the discrete time Power Spectral scribed to sampling used prior are used on filters is widely of two types are digital filters. In-line analog filters therefore signals and are There density p421]. in the component density expressed as (Heart Rate) Hertz As a density, total is there is no power at a single power contained obtained limits tion is of by between integration the band. Since the equivalent to 37The frequency = 1/T where the actual resolution T is the by the dataset is frequency record length. by over some and some frequency high composed of band. The frequency filtgh, density function between the discrete is determined but frequency, fiow, power spectral a summation of subsequent multiplication A/ of low some frequency the frequency discrete values, this integra values contained within the band and resolution37. the inverse of the total length of the time record or Appendix B Rabbit Endotoxin Methodology from Strong a Study Grant Proposal Results Sections and Grant Proposal to the Children's Research Center entitled Heart Rate Power Spectrum During by Septic shock principle Brahm and Catecholamine Changes in the Rabbit investigator Goldstein, 95 M.D. STRONG CHILDREN'S RESEARCH CENTER GRANT Heart Rate Pover Spectrum and Catecholamine Changes Durina Septic Shock In the Rabbit Investigator: Principal Co- Brahm Goldstein, M.D. (Pulmonology/Critical Care) Niels Lund, M.D. Ph.D. (Anesthesiologyjcrltical Care) Paul Woolf M.D. (Endocrine-Metabolism Unit) Mark Kempski. Ph.D. (Mech. Investigators: , Engineering, R.I.T.) SPECIFIC AIM The autonomic nervous system, composed of the sympathetic nervous system and the nervous system, is the principal integrator of cardiovascular homeostasis during stress. Pover spectrum analysis of heart rate variability is a parasympathetic quantitative proven, noninvasive measure of sympathetic and parasympathetic Plasma catecholamine levels correlate with the degree of sympathetic activation during sepsis. We hypothesize that temporal changes in power spectrum analysis of heart rate variability and catecholamine levels predict the development of autonomic failure and subsequent cardiovascular decompensation. The model we will use is E. coll Induced septic shock in the rabbit. This information will define the mechanism and timing of autonomic failure in septic shock. The significance for medical care will be early prediction of cardiovascular collapse and a method of monitor ins treatment during septic shock. Specific aim: To define heart rate pover spectrum and catecholamine changes as a measure of autonomic failure in endotoxin-induced septic shock in the rabbit. acvtivity.(l) RATIONALE Background Septic shock Is a life-threatening complication of serious bacterial infections. Septic shock Is a major cause of irreversible hypotension, multiple organ system dysfunction, and death. Endotoxin is one of the principal bacterial initiate the septic shock syndrome in gram-negative bacterial is characterized by the development of cardiovascular abnormalities including a high cardiac index, low systemic vascular resistance index, and myocardial dysfunction. that components Septic sepsis. shock Heart Rate Pover Spectrum Analysis Power spectrum analysis of heart measure of sympathetic and variability is rate parasympathetic activity. a quantitative (1-3) By noninvasive monitoring heart rate fluctuations In hemodynamic ?arameters can be performed. (1-3) Periodic fluctuations in heart rate occur at owfrequencies (0.01-0. IS Hz) and at high-frequencies (0.25-1.00 Hz). The two principle branches of autonomic cardiovascular control (the sympathetic and ?arasympathetic nervous systems) are reflected in heart rate power spectra by a owfrequency peak around 0.01-0.15 Hz and a high-frequency peak around 0.25-1.00 Hz. The low-frequency fluctuations are a result of heart rate variability due co blood pressure fluctuations at this frequency. The lov-frequency fluctuations are and respiratory mediated by rate combined quantative variability, and sympathetic analysis parasympathetic of activity at rest while The beta -sympathetic activity predominates during stressful conditions. high-frequency fluctuations (>0.15 Hz) are under parasympathetic control and are associated with HR variability as a result of the respiratory cycle (respiratory sinus arrhythmia) . (1-3) has been used to evaluate autonomic function heart failure, congenital heart disease, chronic renal disease, diabetic peripheral neuropathy, mild hemorrhage, and brain injury. (1-3) Heart rate power spectrum analysis is useful In the assessment of Heart in humans spectrum rate pover with chronic analysis congestive normal physiologic and pathophysiologic changes in the autonomic nervous system and as a diagnostic and prognostic tool. (1-3) Patients with congestive heart failure were found to demonstrate derangements in heart rate modulation at a frequency diminished with abnormal baroreceptor reflex responsiveness suggesting but normal sympathetic cardiovascular tone. (2) Experimental animal models Include the dog and rat. Pover spectra of arterial blood pressure In spontaneously hypertensive rats indicate an Impaired control of normotenslve controls. (3) sympathetic drive to resistance vessels compared to consistant vagal Brain Injury Heart Rate Pover Spectrum and Catecholamine Data in Acute Goldstein and Woolf are studying the relationship betveen plasma Preliminary "suits in pover spectrum changes. catecholamine levels and heart catecholamines reflect control subjects and acutely brain Injured patients shov low-^?^60^^6-"."",?^*^,?!?;?0^* Preliminary Drs. .rate sympathetic presynaptic activity while postsynaptic sympathetic activity in the Lov-frequency absence of heart rate measurable CatecechJlamines activity during are acute, power changes hemodynamic th. malor stressful cardiovascular reflect 7em Increased fl"?"*"!*** * sympathetic activity ,, a?5>the In the changes. modulatory situations. substancesof In numerous J^^USSLJT^^ species, including man ana plasma rabbit, catecholamine (norepinephrine, epinephrine, and dopamine) correlate vith the degree of sympathetic activation been demonstrated to decapitation, head trauma, hypoxia, sepsis, levels have during While resting and hemorrhage. levels have been established In the rabbit, levels during sepsis are Dr. Woolf is an expert in the field of catecholamine research and will insights into the association betveen catecholamines and lov-frequency heart catecholamine unknown. provide pover. rate Hypothesis We hypothesize that the hemodynamic changes of which occur shock septic during the development are a result of failure of the autonomic nervous system to for the cardiovascular abnormalities. We propose that pover spectral compensate heart rate variability will provide a means to predict the development failure and subsequent cardiovascular decompensation and shock in a rabbit model of endotoxin-induced septic shock. We will use heart rate pover spectrum analysis to determine the mechanism and timing of autonomic failure. We use plasma will catecholamine levels as a marker of sympathetic activation during sepsis and correlate catecholamine levels vith heart rate pover spectrum analysis determinations, specifically lov-frequency pover. a measure of sympathetic activity. tfe will test the efficacy of pover spectral analysis in monitoring the autonomic response to a therapeutic infusion of an exogenous catecholamine, dobutamine, once shock and hypotension have developed. of analysis of autonomic The Rabbit Model The rabbit is a veil established model for the study of endotoxin-induced septic ideal model for our study. Dr. Lund has previous experience vith this model (4), and is currently using a similar model to study tissue F02 levels during septic shock. We have validated the technique of pover spectral analysis in the rabbit model in Dr. Lund's laboratory (see Fig. 1). The rabbit is large enough shock co (4) and an accomodate arterial, central venous and pulmonary artery catheters which will physiologic monitoring. In addition, we will collect systemic arterial, pulmonary arterial, and central venous pressure data for future pover spectral analysis as Dr. Kempski develops the necessary algorithms and software for pressure waveform analysis. This data will provide additional understanding of cardiovascular control mechanisms such as ventricular-vascular coupling and autonomic control of the pulmonary circulation and form the basis for future provide adequate Investigations and funding. We will use an acute model of septicemia rather than a more protracted model such as cecal ligation and perforation. This model provides for a clear and rapid demarcation betveen baseline measurements and the development of sepsis and shock. We chose to evaluate pharmacologic intervention vith dobutamine (a strong beta-1, veak beta -2 and very veak alpha agonist) for tvo reasons. The first is the dobutamine corresponds to the parameters that pover spectrum been demonstrated to measure, i.e. beta- sympathetic activity. Secondly, dobutamine is commonly employed in the care of critically ill patients vith sepsis c 5 syndrome and septic shock. We vill administer dobutamine at tvo concentrations , tncg/kg/mln and 20 mcg/kg/mln at the onset of significant hypotension (blood pressure decrease to > 2 standard deviations from baseline). These concentrations correspond mechanism of analysis has action of . . *-... . ,-- . -~ low and moderately-high clinical dosages, respectively. We are currently generating heart rate pover spectrum data using the methodology described belov. The rabbit has been validated as a model for heart rate pover spectrum analysis in Dr. Lund's laboratory (catecholamine levels are pending). The co methodology rat. (1-3) i -a* of validation Dnder is similar pentobarbital to that anesthesia previously i -r in the human, used (see METHODS) heart .as rate spectral dog, and analysis ^ cT-ta tnf !-: r^te'i .a^Mt^.fo .1 rtaTf*Cf raniUCT Fig. I LA Fig. < IB C i.a* -p . .'r -..4- mcaiicMcv Fig. (Ht.tn 1C performed on 5 normal adult rabbits [Fig. 1. Pover spectral density (PSD) (beacs/min 2/Hz) (y-axis) plotted vs. frequency (Hz) (x-axis)]. Figure 1A demonstrates a pover spectral plot a normal in anesthetized adult rabbit. density 12,r f roqizency pover (LFP) at 0.010-0.15 Hz and the high-frequency pover (HFP) at Jng 0.25-0.50 Hz (the respiratory sinus arrythmia) are labelled. Pharmacologic blockade of first the parasympathetic and then sympathetic nervous system vas done with atropine (0.01 mg/kg) and atropine ? propanolol (1 mg/kg). The pover spectral was plots shov ablation density (Fig. IB). High- and complete autonomic of high-frequency pover after atropine administration lov-frequency pover are essentially totally ablated after blockade vith atropine and propanolol (Fig. 1C) . METHODS OF PROCgDimg A. Model A total of 20 Nev Zealand vhite adult rabbits vill be studied (10 control/sham Injection vith saline and 10 septlc/E. coll endotoxin Injection). Weight will be between 2.7-3.1 kg. Male rabbits will be used to exclude any sex specific differences. B. General subject assessment and management All medications and their type, amount and frequency of administration are recorded. Figure 2 shows the timeline of the study. Pentobarbital, a short acting barbiturate, will be used for Induction and maintainence of anesthesia. Pentobarbital is a myocardial depressant and will result in a moderate increase in cardiac sympathetic tone. This will not interfere vith spectral analysis or catecholamine determinations as the degree of sympathetic stimulation is Insignificant compared to septic shock. Maintainence anesthesia vill be via administration of intravenous pentobarbital 5 mg/kg iv q 20-30 min prn tachycardia or agitation. Euthanasia is performed at the conclusion of the experiment as the animals are not expected to survive the septic shock. C. Data Collection All data are collected and compiled on standardized forms for data entry (Appendix A). Clinical data include age and veight. Cardiopulmonary data (heart rate, respiratory rate, blood pressure, central venous pressure, pulmonary arterial pressures), catecholamine levels, and heart rate pover spectrum data vill be recorded at time 0 and then q 5 minutes until the development of hypotension (average 20-30 minutes or 4-6 recordings). These measurements vill be repeated infusion of 5 mcg/kg/mln and then during dobutamine infusions, once 5 minutes after 5 minutes after the dobutamine is increased to 20 mcg/kg/mln. (See timeline diagram in Fig. 2). EKG, respirations, and arterial/venous pressure data vill be stored on 44 megabyte Bernoulli cartridges. Pover spectra vill be processed and analyzed at che conclusion of the experiment. D. Catecholamine Levels Serum catecholamine are dravn from indvelllng venous catheters. Handling and Dr. Woolf. (5) Dobutamine infusion assay of samples have been previously described by pressure liquid will not Interfere vith epinepherine or norepinephrine high dobutamine infusions are inna curate chromatography assays. Dopamine assays during personal communication) and vill not be run. (ref. - Flguro 2. Tinlin VIVARIUM of study. EQUILIBRATION INDUCT ANESTHESIA (PENTOBARB IS MG/KG IH) VIVARIUM BASELINE MEASUREMENTS (VITAL SIGNS, PSA, INJECT NaCl/ ENDOTOXIN CATECHOLS) HYPOTENSION (BP DEC > (L3137 1.5 MG/KG) -130 -110 TIME (MIN) -95 -33 -S 0 EUTHANASIA (PENTOBARB 16S MG/KG) 65 DOBUTAMINE S MCG/KG/HR X 5 MIN THEN 20 MCG/KG/MIN X S MIN ANIMAL PREP. (IV, TRACHEOTOMY, ARTERIAL/ CVP/ PA CATHETERS) 2SD) CONTINUOUS MEASUREMENTS Q 3 MIN THROUGH DOBUTAMINE INFUSION (VITAL SIGNS, CATECHOLS) E. Pover Spectral Analysis We use a modification of the methodology described by Akselrod et al (3) and developed by Drs. Goldstein and Kempski. The instantaneous heart rate and rate are recorded from a standard lead II EKG using Hevlett Packard respiratory Monitors models 78213C and 78212D and collected for 256 sec. Data are collected and analyzed using an AST Premium 386/25 PC in conjunction vith a Data Translation 2801A data acquisition board vith sampling at 1 kHz. EKG R waves are detected and a nominal 256 sec instantaneous heart rate time series is constructed. A heart race variability dataset is obtained by subtracting the average heart rate from the instantanteous heart rate followed by linear interpolation. The heart rate variability dataset is passed through a Blackman lov-pass filter (5 Hz) and a Hanning vindov to produce the pover spectra using a modified Asyst Data Acquisition and Analysis Package. The integrated spectral density (area) and peak amplitude symmetric about the respiratory frequency, usually 0.25-0.40 Hz in man and 0.25-1.0 Hz in the rabbit, are used as a measure of parasympathetically mediated respiratory sinus arrhythmia. The density and peak amplitude around 0.01-0.15 Hz are used to quantify beta-sympathetic mediated HR fluctuations. F. Statistical Analysis The data base are managed using INGRES software running on a VAX cluster computer system of the University of Rochester Computing Center. The primary database is downloaded and managed in SAS after transferral to a VAX 8350 owned by the Division of Biostatistics. Stastlcal methods that are useful Include analysis of variance and multiple linear and logistic regression. Subjects are studied Longitudinally. Changes in vital sign* and cardiovascular parameters (as described in parts B and C) are correlated with catecholamine levels and power spectrum data and are used to determine he specificity and sensitivity of these measures. We expect to observe an Increase between 50% and 1000X in lov-frequency pover meesures during the development of septic shock and hypotension. During treatment vith dobutamine, we expect the lov-frequency pover to decrease proportionately with a return towards normotension. For longitudinal studies, repeated measures of analysis of variance and covariance are used. Statistical analysis of pover spectrum data are performed as described by Shannon et al.(l) SIGNIFICANCE OF THE RESEARCH This project is a unique collaboration of medical scientists from Pediatrics (Dr. Goldstein), Anesthesia (Dr. Lund). Medicine (Dr. Woolf) and Engineering (Dr. Kempski). Each has extensive experience in their own field. Preliminary data assure successful These pover completion studies spectra and vill these protocols. provide pioneering of catecholamine levels data vith the by correlating changes development of septic in heart in shock race the These data vill provide understanding of the mechanism and timing of autonomic failure during the development of septic shock. We predict pover spectral analysis of heart rate variability vill enable us to assess the development of autonomic failure and cardiovascular decompensation prior to the onset of any measurable hemodynamic changes* If this technique proves valid, then early therapeutic intervention based upon pover spectral data vith fluids or vasoactive agents may prevent or ameliorate the development of septic shock, hypotension, and multiple organ system failure. The data obtained from this study vill be preliminary data for grants to the American Heart Association and the NIH (Biomedical Research Technology Grant). We believe this research vill lead to therapeutic interventions in patients vith autonomic failure and reduce morbidity and mortality. rabbit. , REFERENCES: L. 2. 3. 4. 5. Shannon DC. Carley DW. Benson H. Physiol 1987; 253:H874-H877. Akselrod S, Ellash S, Orna 0, et Aging of modulation Hemodynamic al. of heart rate. regulation Am J in SHR: inv?sU8*Slon by "Pc"l analysts. Am J Physiol 1987; 253:H176-H183. Saul J?, Yutaka A, Berger RD, et al. Assessment of autonomic regulation in heart failure by heart rate spectral analysis. Am J Card f-fS"1?, c?582sFrIS r 1988; 61:1292-1299. Guiterrez G. Lund N, Pallzas F. Rabbit skeletal muscle p02 during hypodynamic sepsis. Chest 1991 (accepted). Woolf PD, Hamil RW, Ue LA, et al. The predictive value of catecholamines in J Neurosurg 1987; 66:875-872. assessing outcome in traumatic brain injury. Appendix A DATA ENTRY FORM Heart Rate Pover Spectrum Changes During Endotoxin Septic Shock in the Rabbit Subject Identification #: Clinical Data: Weight: Age: Data Collection on / : (kg) / Time: hypotension infusions of and minutes then 5 min (repeat q 5 5 and 20 after min dobutamine). Cardiopulmonary data: Heart rata: Respiratory rate: Blood pressure: Central venous pressure: Pulmonary arterial pressures (PAP/PCWP) : Catecholamine levels : Epinephrine: Norepinephrine : Dopamine : Pover spectrum analysis: Lov-frequency pover (0.01-0.15 Hz): 0.01-0.04 Hz 0.04-0.07 Hz (0.15-1.0 Hz): (0.01-1.0 Hz): High-frequency Total pover HFP/LFP+HFP LFP/LFP+HFP pover ratio: ratio: amplitude area area amplitude area amplitude area amplitude until mcg/kg/mln srea Appendix C Related Published Abstracts 1. Assessment in pediatric 2. Heart rate function brain injury. [14] power brain death. 3. The of autonomic injury 4. Heart 5. Heart during and cardiovascular brain death. state severe brain injury and in children following severe [16] rate power spectral changes rabbit. in changes rate spectral analysis [15] autonomic brain spectrum heart by during endotoxin shock in the [17] rate power spectrum endotoxin shock and in the plasma rabbit. 101 [18] catecholamine changes THE AMERICAN PEDIATRIC SOCIETY 1991 THE SOCIETY FOR PEDIATRIC RESEARCH ABSTRACT FORM ADDRESS CORRESPONDENCE TO: Brahm Goldstein, Name Box 667 Address PRESENTATION FORMATS ACCEPTABLE TO THE AUTHOR: M.D. (choc* all 22465 Goldstein. First Author: B. IWW.MU4 that apply) URMC Urn la EBgajte lor On. Chaot 601 Elmwood Avenue 14642 Rochester, NY x of Thaaa Awonto All Nohania Bowo Aonl In CarsloloBy Poster Symposium Feoow'a Boolo Raaeenol Amort Poster FoSoo/o CTlfilMl Billirit Award Platform Mm Omoor lliiiirr* Aart (716) 275-6542 Telephone N Serial Number: VWsseVjf HeWeVCan AMMfw SUBSPECIALTY CHOICE (Cheek Only One) OF AUTONOMIC FUNCTION BY HEART RATE SPECTRAL ANALYSIS IN PEDIATRIC BRAIN INJURY Donna DeKing Kempski David Mark Brahm DeLong Goldstein. (Spons. by Edward B. Clark). Univ. Christopher Cox. Paul D. Woolf of of Rochester School of Medicine , Strong Memorial Hosp , Depts Rochester and and Rochester, NY, Medicine, Neurology, Feds, ASSESSMENT flrlnlaara.nl Medicine Behavioral Pediatrics X . . . Cardiology . . . Critical Can Developmental Biology Devetopfliental Pharmacology ___ Dyaoiorphology 4 Institute of Technology autonomic associated with cardiovascular is Brain injury dysfunction. Low-frequency (0.01-0.15 Hz), high-frequency (0.15-0.5 Hz) and total heart rate spectral power (0.01-0.5 Hz) are measures Teratology of flaaliiiaiileiiilinn 4 He outcome. patient injury (7M, 5F) (mean 12 8.9+5.9 studied age ICU. Pediatric the to admitted with correlates analysis spectral and brain with 0.1-16) range years, Pediatric Education by heart brain injury patients consecutive hypothesized rate of severity General Pediatric* 4 We respectively. measured as Nutrition parasympathetic, and total autonomic that autonomic dysfunction sympathetic, cardiovascular activity, Preventive Pediatrics - Admitting head + multiple trauma (n-3), rate Heart hemorrhage intracranial and anoxia (n-2) (n-2), Glasgow Coma Score (GCS) were obtained on and analysis spectral days 1,2,3 and weekly thereafter. Glasgow Outcome Score (GOS) was diagnoses head were: (n-5), trauma . Hematology 4 Oncology laununoiogy recorded Infsctlous Dtsoeooo Mstahoflsia 4 Diabetes Neonatology Neonatal * with Qonoral follows: (n-4) We . We compared data. Data GOS GCS, and patient analyzed were using Pearson correlation coefficient, logistic GOS were as Poisson regression (GOS). and analysis recovery (n-5), found (n-0) persistant direct a state vegetative between correlation (n-2) (n-l), and disability moderate , , day 1 GCS severe and death both (r-0.79, p-0.03) and total (r-0.79, p-0.002) power. maximum of levels low-frequency and maximum total power (p-0.03). the study were associated with increased survival levels of maximum low-frequency power were associated with and power related total (p-0.05). Thus, low-frequency GOS low-frequency lateiunology Higher 41 during Higher better Neonatal Nutrition 4 Metabolism Naonatal good disability Epidemiology Follow-up Neonatal (survival), regression Cardiology discharge. spectral deviation, mean+standard Naonetal 4 hospital upon survival directly with Pulmonology to of severity injury neurologic in outcome and children brain Injury. Nephrology Neurology Pulmonology Sponsoring Type Name or Author Member: Signature with abstract typed within tha Abstract Submission Fss METHODS OF PAYMENT $25.00 for - ~X ~Cradtt Card- each abstract ACCEPTABLE ARE (Pleaoo ^Order. (Ma*, cWo/MonJy X Viae unfolded copies of Clark, M.D. 32IMSI box. Do not submitted. fold. (Detach Submit only one abstract with and return paymant option accompanying form - malarial to APS/SPR). U.S. CURRENCY MaeterCard aach envelope. ONLY. DRAWN ON A U.S. BANK. American Express ...... _ ?'(Must _, with abetraet aerial .. # complete toon below for this type . copied onto ... .. . the back. author.' nam- and abstract aenal number on PREPARATION OF YOUR ABSTRACT ARE ATTACHED. DETAILED INSTRUCTIONS FOR THE ... ~ .o qP-..tT=c = n " "=rn ... DO NOT SEND RY AIR EXPRESS IS ACCEPTABLE. In below). chock on>: crocks payabl. Abstract Form aetf-eddressed (unsealed) envelope Ons copy of folded abstract In a STAMPED, Type tha abstract till., SeH-eddreeoed and STAMPED 4x6 Index or post card. 10 B. ABSTRACT MUST BE RECEIVED BY JANUARY 3, 1991. ABSTRACT SUBMISSION CHECKLIST Origln.1 Abstract Form Edward lha back. of paymant). AMERICAN ACADEMY OF PEDIATRICS SECTION ON critical care INSTRUCTIONS: Capitalize title. List authors (Presenter's name first), degrees, institution, city, state, ^nnlir^hla applicable Single-space ? Paper typing. all being Stay within Indicate FAAP where border. submitted to another scientific society for DEADLINE FOR SUBMISSION IS 4 zip. ^^ 15> consideration (no penalty). 1991 ABSTRACT OF PAPER List name, address & phone Presenter number of Brahm Goldstein, M.D. Box 667 University of Rochester Medical Center 601 RlmunnH HEART RATE POWER SPECTRUM CHANGES IN SEVERE BRAIN INJURY AND BRAIN DEATH Brahm Goldstein, MD, FAAP, Mark H. Kempski, PhD*, David J. DeLong*, Donna E. DeKing, Christopher Cox, PhD, Paul D. Woolf, MD, Univ. Rochester Medical (Center, Rochester, NY 14642 and 'Rochester Institute of Technology, Dept. Mech. Engr. Avpnnp 14642 Rochester, NT 716-275-6542 S Academy Fellow ? Resident Fellow D Resident Non-member ? Non-member INTRODUCTION: Brain injury is associated with cardiovascular autonomic dys function. Very low-frequency power (0.01-0.04 Hz) and mid low-frequency power (0.04-0.07 Hz) are measures of cardiovascular sympathetic activity while high-fre quency power (0.15-1.0 Hz) measures parasympathetic activity. We hypothesized autonomic cardiovascular activity, as measured by heart rate power spectral anal ysis, was decreased in patients with brain death compared to those patients with severe brain injury but not brain dead. METHODS: We analyzed heart rate power spectra in 4 brain dead patients and compared the results to 4 patients with Glasgow Coma Scale < 6. Heart rate, respi ratory rate, blood pressure and power spectral data were recorded. We performed cold pressor testing on the brain dead patents to evaluate the autonomic cardio vascular response. Cold pressor testing was performed by ice-water immersion of lone hand for 4 minutes with vital signs and power spectral data recorded during the last 2 min. of immersion. Data were analyzed using mean, standard deviation, and paired t-tests. Presentation 3"' GCS Projector VHSVs" %- BETA ? Proiectlonist ? are expressed as mean (+ standard 2x2 Slides D Overhead ? RESULTS: Data will need: 147(33) 148(32) Reap, 19 (8) 13 (4) 13 (4) 86 (7) 74 (27) 70 (26) rate (per min) preaaure power Box 93 Boston, MA 02111 low-frequency power <bpm2/Hz) 00813 (00881) (bpm2/Hz) High-frequency .01499 (02438) (bpm2/Hz) MM power 00995 (.00718) DEADLINE Mav 15, 1991 presaor 00020 00015 (.00018) (00019) .00001 (.00001) .00133 (.00225) 00001 (.00001) 00130 (00224) Patients with GCS = 4-6 had very low- and mid low-frequency power spectral val 2-4 orders of magnitude greater than brain dead patents. Patients with GCS = 3 had values one order of magnitude greater than brain dead values. Cold pressor testng in brain dead patents resulted in no change in power spectral values. CONCLUSION: Brain death results in near undetectable levels of very low- and mid low-frequency heart rate power. There is a significant difference in autonomic cardiovascular actvity between patents with severe brain injury and brain death. There is no autonomic cardiovascular response to cold pressor testng in brain low- and mid death. Thus, near undetectable values of very low-frequency heart rate power in conjuncton with cold pressor testng may prove to be a reliable diag ues IMPORTANT ? cold Hg) Very low-frequency Kristan M. Outwater, MD New England Medical Center Hospitals 750 Washington Street Brain death 117(23) (mm Send to: deviation). Brain death Heart rate (bpm) Mean blood Other < nostic test for brain death. THE AUTONOMIC CARDIOVASCULAR STATE IN CHILDREN FOLLOWING BRAIN INJURY AND BRAIN DEATH Brahm Goldstein, MD, Donna E DeKing, David J DeLong, Mark H Kempski, PhD, Christopher Cox, PhD, Mary M Kelly, RN, Diane D Nichols, Paul D Woolf, MD. Univ. of Rochester School of Medicine and DepL of Mech. Eng., Rochester Inst, of Tech. INTRODUCTION: Brain injury is associated with autonomic cardiovascular dysfunction. Brain death results in complete cessation of efferent autonomic impulses from the central nervous sys tem. We hypothesized that autonomic cardiovascular activity, as measured by heart rate power spectrum analysis test (CPT), with severe heart rate (PSA), plasma norepinephrine (NE) levels, and the response to the cold pressor be decreased or absent in patients with brain death when compared to patients brain injury. Low-frequency heart rate power (0.01-0.15 Hz) and high-frequency would power parasympathetic (0.15-1 Hz) were measured as parameters of cardiovascular sympathetic and activity, respectively. METHODS: We analyzed cardiorespiratory parameters, PSA, NE, and response to CPT in 6 brain dead and 3 patients with Glasgow Coma Scale (GCS) < 6. HR, RR, BP, PSA, and NE lev els were recorded. The CPT was performed by ice- water immersion of one hand for 4 min. with vital signs, PSA, and NE obtained during the last 2 min. Data were analyzed using mean, SD, log transformation, paired and unpaired t-tests, Mann-Whitney and Signed Rank tests. RESULTS: GCS < GCS 6 + N 3 Age (years) 3.6 3.7 HR (bpm) 132 + 49 RR (per min) 32 15 Mean Blood Pressuire 88 26 (mm Hg) power 0.00603a High-frequency power (bpm^) 0.00150 422 lb Norepinephrine (pg/ml) Data are expressed as mean +_ SD. cold pressor 6 6 5.1 +7.2 - 133+48 38+13 88 30 137 36 17 + 8 67 24 137 + 37 17 + 8 65 22 0.03486 0.00022a 0.00024 0.02117 0.00011 0.00017 0.00573 0.00097a 0.00251 0.00183 4318 103 a p < 0.0001 (n 0.00097 = 0.00181 135 3) 52 28 5542 5181 Brain death + - 0.08442 (bpm^) pressor 3 0.06463a Low-frequency Brain death 6 < cold b p < 0.05 lowfrequency power (LFP). CPT in GCS < 6 patients overlap between groups at 20-100% different from baseline values although were LFP that RR and in resulted in changes not statistically significant. CPT in brain dead patients resulted in no measurable change in car < diorespiratory parameters or PSA. The absolute changes with CPT were greater in GCS 6 pa < patients than brain death. 6 greater in GCS tients compared to brain death. NE was significandy group. either in CPT after There were no significant changes in NE levels There was no CONCLUSIONS: 1 Brain death NE. results . j in abolition of ji , r low-frequency heart rate power as well as reduced levels of . 2. There is no autonomic cardiovascular response to the cold pressor test in brain death. 3. There is a significant difference in autonomic cardiovascular activity between patients with severe 4. Thus, brain injury and brain death. near undetectable values of pressor test may prove to be low-frequency heart rate power in conjunction with the cold a reliable diagnostic test for brain death. HEART RATE POWER SPECTRUM CHANGES DURING ENDOTOXIN SHOCK IN THE RABBIT Brahm Goldstein, MD, Doris R Stair, Richard deAsla, Donna E DeKing, David J DeLong, Mark H Kempski, PhD, Niels Lund, MD, PhD, Paul D Woolf, MD. Depts of Ped, Anesth, and Med, Univ of Rochester School of Medicine and Dept of Mech Eng, Rochester Institute of Technology INTRODUCTION: Septic shock is associated with severe hypotension and autonomic cardio vascular dysfunction. Low-frequency heart rate power (LFP)(0.01-0.15 Hz) and high-frequency heart rate power (HFP)(0. 15-2.0 Hz) are measures of cardiovascular sympathetic and parasympa We hypothesized that temporal changes in heart rate power spectrum (HR PSA) may correlate with the development of autonomic failure and subsequent car diovascular decompensation in a rabbit model of septic shock. METHODS: We studied HR PSA in 9 anesthetized adult male New Zealand White rabbits (6 septic, 3 control). After tracheostomy, internal jugular and carotid artery cathetization, animals were maintained on FIO2 = 0.40. There was a 30 minute equilibration period prior to each experi thetic activity, respectively. analysis Baseline HR, RR, mean arterial pressure (MAP), and HR PSA were obtained. Septic induced by E.Coli endotoxin 1.5 mg/kg iv over 6 min. Controls received 1.5 ml/kg saline. Data were recorded semicontinuously until the onset of severe hypotension (MAP < 65 mm Hg). Dobutamine was then infused at 5 and 20 mcg/kg/min for 10 minutes each. Data were ana lyzed using mean, standard deviation, and t-tests. ment. shock was RESULTS: Baseline HFP was greater than LFP (mean HFP = 0.0524 0.0692 bpm2, mean LFP = 0.01 120.0102, p=0.05). There was no difference in baseline cardiorespiratory or HR PSA measurements between endotoxin and control groups. LFP and MAP remained stable ( 15%) for > 60 minutes in controls; HFP was variable. After endotoxin, LFP decreased (mean A LFP = 0.00450.0067 bpm2. p = 0.03) with a concomitant decrease in MAP (mean A MAP = 21.5+.1 1. 1 mm Hg p < 0.003) in 6/6 septic rabbits. Dobutamine increased LFP and MAP in log , endotoxin treated (mean A LFP = 0.0467+0.0528 bpm2, mean A MAP = 15+17 mm Hg) and con trol (mean A LFP 0.08510.0917 bpm2, mean A MAP 2618 mm Hg) rabbits. There was an inverse relationship between LFP and HFP in 3/3 control and 5/6 septic rabbits. Data from endo toxin treated rabbit #1 are shown in Figures. = = M S a ^ \ ENDOTOXIN fc 0 1 o* -id \/t u z Y DOBUTAMINE CONCLUSIONS: 1 . After the administration of endotoxin, a decrease in MAP along with dicate impending severe hypotension and shock. 2. The baroreceptor reflex remained intact during endotoxin shock. a decrease in LFP may in However, the relationship be inverse of normal, i.e. as activity parasympathetic increased. while decreased hypotension developed, 3. Although not statistically significant, dobutamine tended to increase MAP and LFP in controls to a greater extent than in endotoxin treated rabbits. 4. These results are best explained by inhibition or blockade of beta-sympathetic cardiac receptors, tween cardiovascular sympathetic and parasympathetic was the sympathetic response or decreased release of catecholamines during the development of endotoxin shock. THE AMERICAN PEDIATRIC SOCIETY THE SOCIETY FOR PEDIATRIC RESEARCH 1992 N ABSTRACT FORM WDrot uumeitomkke re Brahm (Ual Nhw InUalal PRESENTATION FORMATS ACCEPTABLE Slnjet, CKv, State Zip) Pediatric Critical Care Umveristy of Rochester, NY 14642 B Goldstein. First Author Goldstein, M.D. Address (Dapi.. Institution, 33402 Serial Number fcheck Rochester Medical School 601 Elmwood Ave all Out tpply) 1 All Poster Symposia Postar T...Dhon.( 275-8138 716i Subspecialty Platform SUBSPECIALTY CHOICE (Chock MUST BE RECEIVED BY: January 3, 199 Only One) Adolescent Medicine HEART RATE POWER SPECTRUM AND PLASMA CATECHOLAMINE CHANGES DURING ENDOTOXIN SHOCK IN THE RABBIT. Behavioral Pediatric* __ Cardiology Brahm Goldstein. Doris R Stair. Richard deAsla. Donna E DeKing. David J DeLong. MaricH Clinical Bloethica Kempski. Rebecca B Tipton. Niels Lund. P;n|l D Woolf (Sports, by Harvey Cohen). Depts of Ped, Anesth, and Med. Univ of Rochester School of Medicine and Dept of Mech Eng, Roch Inst of Tech. Critical Car* Developmental Biology Developmental Pharmaoology ___ _^ Dysmorphology 4 Septic shock is associated with hypotension and autonomic cardiovascular dysfunction. Low-fre quency (LFP)(0.01-0.15 Teratology Endocrinology Epidemiology power spectra and plasma norepinepherine 4 anesthetized adult male Preventive Pediatric* internal jugular cannulation and tra for 60 min. (controls) or until mean arterial pressure (MAP) decreased > 20 mm Hg. Data using mean, SD, log transformation and t-tests. After endotoxin, MAP and LFP de creased but catecholamines were unchanged. HFP decreased with in both groups. * Control (N = 4) Endotoxins = 6) p < 0.05 60 min. Dec. MAP>20 mm Hg Basal were analyzed Pediatric Education Genetlca Hematology 4 Oncology Immunology Infectious Disease* Metabolism 4 Diabetes HR(bpm) 146 MAP (mm 85+5 Hg) Log LFP (BPMA2) Gsnsral Epidemiology 4 Follow-up Neonatal Immunology 179 +-13 77 18* + 0.89 -4.13 + -2.78+ 1.16 -5.40 + 92 + 111 40 159 2 + + -4.78 LogHFP(BPMA2) NE (pg/ml) EPI (pg/ml) DA (pg/ml) Neonatal Cardiology Neonatal (NE), epinepherine (EPI). and dopamine (DA) levels in 10 min. after carotid and recorded General Pediatries 4 - NZW rabbits. 30 activity, respectively. We studied changes in heart rate cheostomy, E. coli endotoxin (1.5 mg/kg) or saline (1.5 ml/kg) was infused over 6 min. Data were Gastroenterology 4 Nutrition Neonatology Hz) and high-frequency heart rate power (HFP)(0. 15-2.0 Hz) measure cardio vascular sympathetic and parasympathetic 82 0.724 0.97* +45 224 62+ 0.93 -3.90 + 0.90 127+118 -4.85 + 35* 20 7 + + + 21+0 21+0 28+ 17 41+0 54+16 50+ 22 5* 1.98* -6.35 + -5.33 + 0.73* 114+ 91 26+8 66+59 We conclude that after endotoxin administration a decrease in MAP and LFP with no increase in cate cholamines indicates impending shock. We suggest that inhibition of sympathetic nervous system ac 4 Hematology Neonatal Infectious Olssssss tivation Neonatal Nutrition by endotoxin contributes, at least in part, to the development of endotoxin shock. 4 Metabolism Neonatal Pulmonology Nephrology Neurology Pulmonology Sponsoring or Tvps Name Author Member Signature WTUHH) RtStARCT 8TMHBW WITH UniUOIUP These Joint Saaaiorta will ba hald on Monday afternoon. May 4. 1992. If you want your abstract to you must ba eonaidarad for any of tha following sessions, H*j Check if abstract accompanied by is eligible for one of these support materials. (See Awards. Must be page 5 of instructions) Indicate so hare. Richard 0. Rowe Award In AIDS and Retroviral Dis Cytokines. Intarlaukins Genetic Basis of and Mall To: Their Receptors and Fellow'* Clinical Research Award House Officer Research Award Disease Growth Factors. Growth Cardiology Fellow's Basic Research Award Differentiation Student Research Award Northwest Point Blvd.. Elk Grove Vlllane. IL 60009-0675 APS/SPR Prooram Office. P.O. Box 675. 141 Appendix D Sample Program Output for 107 a Normal Analysis EKG Waveform Analysis / Heart Rate Variability Study 02/17/92 13:17:33 FILE Original File Data File Name: : Results COMMENTS RS15-13.DA Comments: 1> HR153 RR26 BP84/68(77) CVP4 2> 3> 4> 5> 6> 7> 8> #Chnls 4 File: RS15-13.DAT SEARCH File Subfile Size: Scan Window Size: Windows Subfile: per Zoom Window Q-R-S Complex Maximum Peak Maximum Instantanous Digital Smoothing Voltage Threshold: cutoff Total R-peaks Accepted: Average Heart Rate: Total Record Time [R to Total resolvable Removed IHR *** 8 Points Intervals Points 2.70000 R] Points BPM 15.99076 (IHR. VALUES 668 IHR Values array) Removed *** BPM Hertz 152.33060 .00781 detected Milliseconds 326 128.07401 : Time: (msec) (msec) (msec) (msec) Volts RESULTS Frequency: R-peaks NO Points 5.00000 frequency: Frequency: original Points 128 468.75000 Heart Rate: ANALYSIS Nyquist 1024 128.00000 Proximity: 08/01/91 CRITERIA 95 Size: Minimum Smallest Date: Seconds Hertz Hertz Points 12:01 Band Number: Band Name: Lower Edge Frequency: Upper Edge Band PEAK Frequency: Frequency: Band PEAK Value Band PEAK .01562 .03904 .01562 .21818 Power Band TOTAL Power Band Number: Lower Band VLFP ,00170 ,00425 Name: Hertz Hertz Hertz (actual) (actual) Frequency: 04 68 5 Hertz Frequency: ,06246 Hertz Band PEAK Frequency: 04685 Hertz Band PEAK Value 11526 BPM"2/Hertz Band PEAK Number: Band Name: .00090 BPM"2 .00148 BPM*2 (actual) (actual) Lower Edge Frequency: .01562 Hertz Edge Frequency: .14835 Hertz Band PEAK Frequency: .01562 Hertz Band PEAK Value .21818 BPM*2/Hertz Band PEAK Power .00170 BPM*2 Band TOTAL Power .00832 BPM~2 Number: Band Name: HFP Hertz Edge Frequency: .15616 Frequency: .49971 Hertz .46848 Hertz Band PEAK Frequency: Band PEAK Value 1.04970 Band PEAK Power .00820 BPM"2 Band TOTAL Power .04840 BPM'2 Band Number: Band Name: ,07000 Hertz Hertz (ideal) (ideal) HFP (actual) (actual) 01000 Hertz 15000 Hertz (ideal) (ideal) (actual) (actual) 15000 Hertz 50000 Hertz .15000 Hertz 2.00000 Hertz (ideal) (ideal) BPM"2/Hertz 15-200 Lower Edge Frequency: .15616 Hertz Upper Edge Frequency: 1.99884 Hertz Band PEAK Frequency: .46848 Hertz Band PEAK Value Band PEAK Power .00820 BPM"2 Power .07404 BPM~2 Band TOTAL .04000 15-50 Upper Edge Lower (ideal) (ideal) LFP Upper Band Hertz MLFP Edge Band Hertz .04000 BPM~2/Hertz BPM*2 BPM"2 Upper Edge Power Band TOTAL Power .01000 1.04970 (actual) (actual) BPM*2/Hertz (ideal) (ideal) Band Number: 11 Band Name: SPECTRUM Lower Edge Frequency: .00781 Upper Edge Frequency: 15.99076 Spectrum PEAK Frequency: .46848 Spectrum PEAK Value PEAK Power Spectrum TOTAL Power Spectrum 1.04970 Hertz Hertz Hertz (actual) (actual) Listing Hertz Hertz (ideal) (ideal) BPM~2/Hertz .00820 BPM~2 .08308 BPM~2 USER-DEFINED/List-Selected Ratio .00781 15.99076 Power TOTAL:: TOTAL Ratios TOTAL POWER 3:3+4 14671 .05672 4:3+4 85329 .05672 3:3 + 5 10104 .08236 5:3+5 89896 .08236 (denom.) J3 CO u X X -Lfl .JO a" N N ft U <A K C 8 e a. z ..9 O a eo a. eo co ft h co a A o u u o w X * 9 ft, z h e CM co *) M s t ft -- -I in H u u . CO H I It) H r) a N CO K 9 I I rl CB N I I I I a 9 HHI u e e ff 3 O o a* J< + r- . o mm vD 0 (SI u m 0 00 CM O H +> -H e Q.M3 o en u m ,a c M am <H 0 1 l> LI PI 9 I I en U H E 1 0 lO ff H U CO 0S P4 Cm CJ 1 I 1 9 SO H <Hia> C5 X w +J I CJ u ii o. 9 9 9 co <MdS> * II 9 SO Li I 9 9 OS J" HHI I JS 9 9 9 9 (ZH/ZvN<ia> t, UJ +> s: s o u u e e E FH $ ^a +> r^ e en u en 0 GO CM CM &)LO AsO p^ ** \D 0 ro u en ft +> O +> -H -H 0 ti H E 1 0 LD E <H OJ CO K >f*>4 > Cm e dS3U jo QSd 9 J* '9 CMui X 9 AD CO H + O K r- z co in H (4 m i 9 9 . 9 i i i i i rr 9 9 9 N CD J1 9> 9 9 9 * X (ZH/ZvNda) AHH <Hd&) u u + 0) e e c 3 O u e-J }* + r^ . -ft e P4 rX VO 0 CM u en a 0 CO +> CM O -H +> E Q*vD O en M en * CM BiLO D 0 H U -H E 1 0 m f= <H U CO K -< p* <M O AUH jo asd 9 T9 *9 CM u X 9 1*0 Z \ K 4 n 9 ..CM CO H 9 H in in VD CM LI K Z O M H a K M ft. (4 LI (ZH/ZvHdS) (ar.iIJ) M u +* E u E s 3 O u P<< ppj ej* * r* pfl en u en pC P* v> 0 CM u en a, +> CM OLD + 0 0 CO CM O <H -H u -h E 1 0 LP C -H OJ CO *K j Cm * dS3H jo QSd * Appendix E Software Design and Program 115 Operating Manual CONTENTS 116 Contents Appendix E Local Table Software Design - of and Program Operating Contents Manual 115 116 Local List of Figures 117 Local List of Tables 118 E.l ASYST Software Usage 119 E.2 The Program Format 120 E.2.1 The Original Program Format 120 E.2.2 The Final Program Format 121 E.2. 3 Program Source Code Development E.3 The Menu-Interface E.4 Using E.5 Additional Features Index of the Application Program the Program for of and a Normal HRV Analysis the Program Layout 122 122 127 134 E.5.1 Graphics Environment Menus 135 E.5. 2 Supplemental Program Utilities 137 of Operator's Manual 145 LIST OF FIGURES List of E-l An 117 Figures Procedure Description Header. The line example of a the @ sign % the with lists those routines lists those sign that this call E-2 listed separately The Main Menu display of the E-3 The Filename. Prompt Window The one. this routines which beginning with line(s) beginning routine calls. LIBSERVRs 123 called are text. The particular The File as running is Transfer Single Channel, 127 comment access to various viewing of the allows line editing, and DOS collected 128 Editor/ DOS Utilities Menu allows examination the of data file. Comments lines in the datafile comments can be edited 129 necessary The Display Subfiles Contained Within data file in the previous The allows menu editing to displays the selection the file same window area where The Edit File Comments edit, then E-9 shown data file a and contents of a E-8 routine The DOS Utilities & Comment Editor Menu data in E-7 filenames. Note the particular routine commands, data file E-6 of from the Main Menu selected E-5 display for entry used using the window is displayed in the title bar. In this case, the Main Menu selection, Transfer Single Channel, is in use. 126 The Routine Processor Window has a vertical space of 12 lines to display name of E-4 the 124 application program selection The proceed. contents of comments are queries a comment example shown is listed. . number relates the . to the figure Modify 131 Status-Comment-#8 stamped' status E-10 The GRAPHING line in a menu allows adjustment of the 'time- data files menu allows 131 various options for plotted graphs: printer hard copy, comment insertion, and entry into the Multigraph environment. The maximum frequency plotted can also be changed for spectral plots. . E-ll The Put Comment Menu, ation and placement of E-12 The MultiGraph the selected two separate graph menu allows display Directory Display from the GRAPHING Menu plotting of allows labels two examination of 136 graphs of processed data on 137 allows the files lists the requested E-14 The Set Search Parameters for the listing by a drive and allows scrolling feature. . . allows adjustment of several parameters during a vertical space of 138 140 during data processing Manual The E-16 Processing Commands used available space on a window allows adjustment of several parameters data processing E-15 The Set Search Parameters window used 135 cre same E-13 The 130 to 18 lines to Menu, selected from the Main Menu, has display additional menu items 141 143 118 LIST OF TABLES List E-l of Tables Listing of descriptions, tines in the E-2 Main Menu names and source file locations of the major rou 123 program selections which items. The items are to input information 'action' classify further or not as grouped as to items rather whether the than user is submenu required 126 APPENDIX E E.l The 119 ASYST Software Usage software package used for this work is ASYST, called (Keithley- A Scientific Solution ASYST Inc., Rochester, New York) and operates on an IBM-compatible personal com (PC) directly from the DOS command line. To invoke some command or implement function in ASYST, a word is activated simply by entering the name of the word at puter some the ASYST those are those words produced System words System base and line. There command fall words are always by the under two system words software package and user-defined words are categories: words for available1 in ASYST: of words used user or programmer. those are two type are the ASYST words supplied with that To use. base system are words and system supplied the with the versatility enhance core overlay ASYST words. software the ASYST software, of its developers included specialty system overlay words in separate system overlay files which can be called up and loaded during processing, when the words they contain are Since only one overlay file can be loaded at any one time, several system overlay files (thus all their words) are able to be loaded into and stored permanently to a basesystem program. This base-system program would then be invoked directly from the DOS needed. command line immediately and all available The developers dures the words, built-in for use at to or user-defined words user-defined words stored nently the DOS in just an command the ASYST the ASYST of those from the command software also system overlays, in that they system words application-specific base-system line). This structure employed was the would be line. to allowed users their write program be can own proce ASYST treats perform complex or repetitive processing. it does as and created and perma (also invoked directly from for the first original program format described in Section E.2.1. The developers own application files, along either only the ASYST overlay files that the with system one application simultaneously. be loaded of However, permanently. files, overlay words defined words program to be resident the system concept in the employed be to users user-defined words. to the their create These overlay constraint of using time, but never both overlay overlay files, application overlay files can not one at a is incorporated by 'permanent' user-defined words an overall program application for the final allowed subject application-specific to be included in the format their would or one system described in the preceding paragraph. Efficient use of application overlays in defined furthermore would contain overlay unlike This software design base-system overlay files. This and current versions of requires some the and all was the the heart other user- user- approach and rate variability analysis application software. The Stack. concept 1 of a stack ASYST actually but is not used The ASYST is similar allows for this the work. to software uses stacks to that removal of of a many plates words store data dispenser in by during a a process called processing. restaurant. Data The are Symbol Table Compaction APPENDIX E 'pushed' down 120 onto the top of the 'popped' to data processing stack prior during ofF and or after processing. Errors that during processing may leave items (numbers or arrays) on the lead to further errors in subsequent may processing if the stacks are not 'cleared'. ASYST includes options for users to program error-trapping and properly occur stacks2 which routines error-handling to smoothly from recover that may errors occur during the exe cution of a procedure. E.2 The Program Format Note: The following runs actually There the were the and the interface, user format, the way the by which the operator program method program. three software program section discussions differentiate between the internally, program operates major essentials of the heart rate the developmental during created describes the versions of the program analysis variability stages of this application The work. formats employed, those previous being, user- defined words, the application-specific base-system, and application overlay files. All three versions of the program employed discrete procedures to accomplish specific tasks. Because of the highly variable nature of the data from individual physiological patients, frequent operator interaction was necessary throughout the implementation the program. The primary reason for this interaction was necessary visual inspection the a physiological procedure implementation and was retained E.2.1 The data to properly processing type start-to-finish select parameters was program approach was adopted in the final format user-defined procedures sufficient for feasible Thus, A discrete undertaking. the initial during of development program versions. for the level into used for the first a single of program original to procedure program some key-combination operating the program, reference by ASYST the uses employed a of Coincidently, stacks, need that to stage of analyze program a user program incorporated base-system. This interface development. was always which mapped this keystroke map a number stack for processing changes used. available for the processing of logical values and character strings. 3The rabbits had very high heart rates and therefore the number subjects. greater than originally anticipated for human the However, rabbits3, necessary format all approach was every the PC keyboard (i.e. <Ctrl-Fl>). keystroke map operator. two types on the specific during complexity version version of application- due to memory constraints resulting from the in memory usage resulted in a change in the 2 a processing. The Original Program Format original program The not subsequent of To for immediate was also numbers and major assist invoked from arrays, in recall and a and a symbol stack of R-wave peaks found was much APPENDIX E 12i keyboard key-combination. This original at the ASYST command line level. At this stage, that errors during occurred procedure and return program control the line command 'stacks' the features more throughout E.2. 2 The ing and second type task words, third/final format employed used used changed. The for the first The final of this utilized was a great curve a which menu Any processed would few be many contain user-defined the was used with memory second vastly im usage was analyzed without difficulty. The the keyboard key-combination to minor changes second The items user inter to improve some procedures final and versions operation of concerned interface for the final user were selected and unhandled errors the then application. the type version Recollection of used a This activated. a avoided. be lost since principle operators of An additional of For example, if Stage 6 primitives number menu the running of program stack Data loss resulting from knowledge a procedure menu of which requires because under an returning program interruption created in the first two as many versions and during menu usage Subsequently, the data being runtime errors primitives4. and use of it, version running these primitives would not be known software. error-handling included involves the processing (words) available the line. This type cluttered using programming the level further for this final occurring in procedure and command reconstructed only with files, which difficulties than just primitives are format overlay Thus to the operator, nothing had really used essentially the same program format as routines were enhanced even to the ASYST ^Program base-6ystem, rates could program program. terminate the therefore had to be by and used keyboard key-combinations became unnecessary and by for new personnel to operate the software was significantly lessened. active menu would only be the improvement to The error-handling the menu interface. could for the invoked procedures were more to incorporate program. but included through interface learning the version of difference between the major system control very little this, and speed. efficiency interface application format, second program very fast heart version of menuing of of major program versions. second version used program many program second program version also entertained use of the Because program grew developed, improved, routines were permanently into it. This proved and subjects with user As the and an application-specific With the introduction the re-started. procedures. of program procedures stored face terminate that line. Error recovery at major loss of data since The Final Program Format specific and be procedures. operated actually command correctable without versatility, error-handling the all of program was a specific procedure would procedure included into the was error-trapping the cleared and the to the ASYST immediately was often be could version of data derived from Stage 5, Stage 6 include basic outside of math operators, array the menuing environment, manipulation at the ASYST will sequence try to procedures, command itself. activate etc. line. These APPENDIX E Stage 5 to processing so the data it obtain approach far because must is 122 of manually the describing (should) to operate, to result E.2.1, the program system and numerous application source code the create files that in the loss names, format creation of and the representative source broken, is the error message Either way, not. total are a the Five 13 other are the of 18 of of separate program these files are used descriptions, support cally for a major cial same group is termed veloped file fall are under and two (2) utility use they only ASYST These utility support support routines major procedure that (1) that routines are system words. developed routines One of routine in the specifi to many are common in procedures are 'common' SERVice Routine (LIBSERVR). Most used designed routines frequently The support. procedure major procedures employed procedures. categories: The specifically designed the LIBrary of and form the found a spe from this group are de these LIBSERVRs Other LIBSERVRs, those only used for one procedure included in the file where that particular procedure is developed. in the file for example, by as of routines a several smaller procedure; major procedures. in the by routines which to files source code overlay final program, listed in order of normal use, are shown in Table E-l. As with any other well structured program, many of the major procedures program are supported operator consists of an application-specific base- filenames, code only be taken Layout and overlay files. Brief actual application is data. of application program. application-specific system-base and in the routines can 'chain' and sometimes one overlay files. There up the total make chain-reaction from the Main Menu. An procedures the problem, occur This and so on. 'prior' When this Program Source Code Development As described in Section used able employed. the necessary activate no runtime errors will E.2. 3 format program displayed sometimes in needs to automatically invoke necessary thetllc.prg. The general appearance and contents of each program source code the main program file (thetlOa.prg). For readability, each file is file is represented in arranged a beginning which describes the file contents, developed within, as well as declarations necessary existing words, procedures (words) The procedure description header, at the beginning of every of locally used variables. procedure in a file, contains a brief procedure description, as well as a list of the routines specific manner with a which own it calls, following This heart those category in the procedure E.3 and large at section routines which procedure description header. call it. LIBSERVRs description header. The called are Figure E-l name procedure always shows listed an under their example of a follows the header on the line. The Menu-Interface section rate the describes in detail the variability screen output are of operation analysis process. included to assist the Application Program Many of the application examples of a new user in software the displayed becoming familiar for a normal menus and normal with the program. APPENDIX E Table E-l: in the 123 Listing descriptions, of names and source PROCEDURE DESCRIPTION Data seconds of collected Convert to Plot 20 Set the major routines NAME FILE Analyze. EKG Recall. Data thetl 3a. prg Compute. IHR thetl4a.prg thetl4a.prg Plot.EKG Set.Parms search parameters dataset processed thet2#a.prg thetl7a.prg thetl2a.prg thetl7a.prg thtl9a.prg thetl2a.prg Plot. Channels Convert. File real values seconds of real values Retrieve SOURCE data Peak detection Compute instantaneous heart Plot instantaneous heart rate Plot.lHR.T rate Patch instantaneous heart rate Patch. IHR Parse instantaneous heart rate IHR. Parse Compute heart Plot heart Smooth heart Compute Plot Set rate rate Window heart rate density density bandwidths powers/ratios report processed dataset activates \ filename is \ a "NULL, \ <D general-use \ */. '/. LIBSERVR: and left the Smooth. HRV variability Store routine Window.HRV power spectral frequency for validity Plot. HRV variability Print the filename type based in the routine Error was .Scrn. thetl4a.prg thetl4a.prg thetlBa.prg thetlBa.prg thetlBa.prg thetlBa.prg Compute. HRV variability variability rate power spectral \ \ of PROCEDURE Get. Data collection Plot 20 \ \ This file locations program. on Compute. PSD thetl a.prg Plot.PSD thetl a.prg Set.PSD. Bands thetl 9a. prg Smooth. HRV thetl8a.prg Store. Data thetl 3a. prg prompt the current str-var: window opcode .file$ terminated, usually On, Error .Scrn. and passed on tests the entered N.stk. for testing. with the <ESC> filenames The If entered it contains key. Off \ Filename. Prompt2 Figure E-l: An @ sign those \ [ file. type example of a lists those routines routines which this -] ( routine. title cur. filename Procedure Description Header. The line that call this routine calls. one. The line(s) beginning LIBSERVRs called are beginning with listed -) the % with sign separately. the lists APPENDIX E Just like many of submenus. layered 124 other programs which utilize For quick The program is in Figure E-2. stages used (Figure during E-2) The item the listing end of of all this the the Main Menu use and appendix. of heart two areas, the rate variability. item selection specific procedures. to The processing which procedures have been for regulating the area, The display and the processing items for menu screen Data Acquisition status area. important action of certain procedures. STATUS LIST cur STORE Data to File . ekg graph peaks ihr FUL NO NO EKG: Plot SET: Search/Program Parms ihr. patch NO EKG: Analyze/Find-Peaks SET: PSD Ranges/Labels hrv NO smooth NO IHR: Plot IHR: Patch/Plot PLOT AREA: IHR: Parse PLOT AREA: (time) HRV: Plot PSD: Plot/smth (auto-fit) PSD: Plot/smth (normal) (user-fit) Top window NO psd NO Create Multigraph psd. power NO Full Channel respira. NO Bottom Display Process Respiration Data REPORT: Print Cover Page Data REPORT: Print Band Data/Ratios RESHAPE Acquis. REPORT: List Band Data/Ratios MANUAL : File freq freq plot Single Commands cutoff EXIT to ASYST Figure E-2: The Main Menu the Menus. the <Home> return key from that or <End> of the volt .95 min. time 256 256 to its a selection parent menu from a menu is usually zoom.w 95 ihr V. 20. #psdbands 5 #psdratio 4 application program. Selecting a menu item requires using the keys) to highlight the desired menu item (<RETURN>). If submenu display 1.0 5.0 min. scan.w EXIT to DOS to information performed as well as current values of Transfer Single Channel Using is the Main Menu status area maintains up-to-date RECALL Data from file File Editor/DOS Utilities of selection of submenus or Pediatric Head Trauma Analysis Application GET: with processing an analysis consists of parameters used at is layered from the Main Menu and its appearance on the The Main Menu provides direct access to all major selection area provides access concerning index an items is included program operated shown invoke reference, there is submenu selection menus, the launches accomplished cursor and a by keys (including then pressing the submenu, returning pressing the escape APPENDIX E 125 key (<ESC>). be to selected Most return the of to its Program Start-up. the program at the DOS being after > by 'Y' response of to the DOS command terminating the invoke a it is invoked and Selection 'y', or No program. can with a single parameter called the EXIT to DOS item operator is All menu selections (2) those items for data responsible fall under two directly which the Main on program and return automatic storage of processed and submenu, of terminate the will line. Note: The Menu Item Types. which item that EKGASYST NOP). Program Termination. followed program possess a menu The Main Menu is the entry point (and normal exit point) of invoked from the DOS command line. The program name used line is EKGASYST command NOP (e.g. C:\ in this menus used parent menu5. Menu, control storage prior data is categories: initiate PC to performed. (1) those items some procedure or action. There are five Main Menu selections e File Editor/Utilities e SET: Search/Program Parms e SET: PSD Ranges/Labels e Create Multigraph e MANUAL: Single Commands [R]. that invoke a submenu which are: [L]6; [R]; [R]; [R]; and, All remaining 22 Main Menu selections invoke some action selections are listed in Table E-2. There are ten perform type some action of operator without input, There the menus such that Prompt Window and and twelve selections selections or 'action'. immediately which which do These require some filename. a usually Special Windows. input user procedure that frequently used throughout they require their own introduction. They are known as the Filename the Routine Processor Window, and are shown in Figures E-3 and E-4, are two windows are so respectively. The Filename Prompt Window input of a is displayed 5If a is filename is necessary. This prominently. submenu possesses an always an option 6The location of Exit but will not the menu be (FPW) As routine ... menu is is for supported item, use of mentioned again item is indicated used most all in Figure seen by E-3, instances LIBSERVRs the <ESC> where operator the type of file to be key to which check return to its used for file parent menu in this discussion. within the brackets, [L] for left side or [R] for right side. APPENDIX E Table E-2: 126 Main Menu items. The items are selections which further classify grouped as to as 'action' whether the items user is rather required than submenu to input infor mation or not. Action IHR: Plot (time) Only (10) Requires User Input [L]+ IHR: Patch/Plot Transfer Single HRV: Plot IHR: Parse PSD: EKG: Plot [L] (normal) [L] Plot/smth (auto-fit) [L] REPORT: Print Cover Page Data [L] REPORT: Print Band Data/Ratios [L] REPORT: List Band Data/Ratios [L] PLOT AREA: Top [R] PLOT AREA: Bottom EXIT to ASYST +The item in the [R] [R] menu (12) [L] Channel [L] GET: Data Acquisition listing is on the [L] [L] EKG: Analyze/Find-Peaks [L] (user-fit) [L] EXIT to DOS [L] RECALL Data from File [R] STORE Data to File [R] Full Channel Display [R] Process Respiration Data [R] RESHAPE Acquis. File [R] left [L] or right [R] side. PSD: Plot/smth Data Channel Transfer Routine Source File Type: ORIGINAL INTEGER <ESC> to EXIT <RETURN> Current filename designation: Enter filename or keystroke: test80.dat Figure E-3: The Filename. Prompt Window name of the particular routine for Current File NONE/SET using the display window case, the Main Menu selection, Transfer Single for entry of filenames. Note the is displayed in the title bar. In this used Channel, is in use. 127 APPENDIX E ROUTINE PROCESSOR WINDOW (ZERO SELECT ONE TRACE to TRANSFER: Select ) 2 ) RES 3 ) PI 4 ) P2 ) P3 5 Figure E-4: The Routine Processor Window has The a vertical space of running is Transfer Single particular routine shown Channel, qUIT) 1 channel: a to EKG 12 lines to display text. from the Main selected Menu. existence, file type, generates this and other things window accepts a which may cause a runtime error. default filename is which The routine which the major routine by supplied 'knows' invoking it, type of this makes normal datafile it As needs. processing faster the top-right at shown since each major procedure of the 'fits' able The FPW pressing the <ESC> key. the is located near the top of display screen. to be terminated the Main Menu and by The Routine Processor Window query to the bottom near E.4 Using This section they would of the describes the be invoked use and during action taken is the It directly heart of 'Selection of subfile number known target disk drives is explained are checked for is an action 56 for the available for another item of comments (64 characters which the Main Menu but is which under the amount of number of acquisition space). created and queried allocated, otherwise, the procedure is offered the opportunity to enter, to the each) relating experiment or patient. and/or The asks .. . operator as the Main Menu. The lost disk filename. After file allocation, the display for. At this point, the tabs being in place. If sufficient space, and write-only is for a filename. A check for duplicate filenames queries is available, the FPW appears file is target the performed and, if there are none, space must 12 lines in item in the Main Menu in Section 2.4.1 desired is and that rate analysis procedure. the RPW in on page and number of of beneath the FPW. subfiles7 channels of is the borders Normal HRV Analysis a selection appearance possesses the borders effects of each selection a normal This screen. major routine within most all procedures within screen, the Program for GET: Datn Acquisition. first also display for display 'fits' this task. The RPW located used information to the prompts or status accomplish is (RPW) the display, what change, number seven of lines channels, APPENDIX E 128 The data is originally collected to the hard drive but is transferred to a Bernoulli the data collection process. This file is the integer data file mentioned in Section 2.4.1. The procedure is completed at this point cartridge after and program control automati cally returns to the Main Menu. DOS Utilities t Comment Editor Menu Plot All Channels 20 - sec. Edit File Comments Directory Directory Directory Directory D: Copy_File C Rename_File B Delete_File A Exit to Main Menu Figure E-5: The DOS Utilities & Comment Editor Menu commands, data file file. comment File Editor/DOS Utilities. At this shows point the resulting the last Selecting filename, data and date collection. can display. menu Finally, the this end of menu and The subfile collection cedure at the data original This and selection be viewed Only item (Exit time of approximate for duration as pressed of the a submenu access item under anomalous points or will are the begin data during to the disposition into acquisition process 20 data in a data the Main Menu. trends. Figure E-5 column of this menu to the Main Menu. an eighth comment line just before is displayed in the RPW. A nominal seconds. collection or <ESC> to terminate the pro the data collection, the of DOS various be described later in Section E.5. 2. 'stamped' minutes and to collected will return program control <RETURN>to If <ESC> is the acquisition) of allows the first two items in the left experiment lasts approximately 4 operator presses point. the ...) viewing is described here. The DOS functions listed are 256 the line editing, the file just created operator will and filled. be queried (at DO NOT USE THE <CTRL-BREAK> KEY COMBINATION TO TERMINATE THE ACQUISITION PROCESS. If <Ctrl-Break> is used, the PC must be re-booted, all data will be lost, and the DOS 'lost' CHKDSK program will have to be used to reclaim the allocated file space (see Table 5 APPENDIX E 12g Plot All Channels 20 sec. This selection is an action item under the File Editor/DOS Utilities Menu. The datafile to be viewed is selected through use of the FPW. After a graphical entry of the of - filename, one for point each channel, (msec.) in the first 20 to dump this graphical display to key. Pressing the key erases 'Q' menu to its the seconds of display displayed8 The data will appear. collected the printer, if the graphical strip plots, represents every data. There is eighth an option 'P' desired, by pressing the display and will return the previous appearance. File Editor/DOS Utilities Menu File: 1 ) Joe Patient 2 ) 3 80 second for EKG record and respiration ) 4 ) 5 ) 6 ) 7 ) ) 8 TEST80.DAT a volunteer #Chnls: 2 lab File: subject TEST80.DAT Edit File Comments Date: Modify 07/19/91 Time: 05:34 Status-Comment-#8 File Comments Display Display Subfiles Contained Therein Exit from Menu Figure E-6: The File Editor/DOS Utilities Menu contents of a allows examination of data file. Comments lines in the datafile Edit. File Comments. This selection is can be the comments and edited as necessary. a submenu item under the File The resulting submenu, which contains a 'win the display, is shown in Figure E-6. Selecting the last Editor/DOS Utilities Menu. dow' near menu the top item (Exit of ...) will return program control to the previous menu (File Editor/DOS Utilities). Display File under 8See of This the Edit File Comments Menu. the description displaying Comments. collected of the Full Channel data. Display selection The selection is window an action just item mentioned from the Main Menu for an alternative means APPENDIX E 130 contains a listing is displayed ments window Display item tioned window stored replaced datafile, the this by of an alternate this which value of zero comment (0) restored will the file and the Selecting previous contents edited. some position complete, the comment. The <RETURN> normally, to its contents of listed. the in the a prompt Entering a parent menu Upon entering a valid the current comment displayed appearance of with a editing key the file 'residue' prompt in Figure E-8. cursor Moving key. The the pressing state of When editing is be pressed to update action. indicated) comments previous appearance. the comment requires must <ESC>(as update ] displays the edited. action and in the existing Pressing 2 appearance. key simultaneously <Insert> key will affect the menu of selected. will result (line number) is to be the <Ctrl> the type a submenu selection under subsequent submenu are shown procedure item is selection this item a submenu will appear with is ready to be the lines. This file comments are terminate further to its and the and 1 Edit File Comments. This is cursor in information relating to menu Contained Within Edit File Comments Menu. to shown window, INTEGER DIM[ 1024 type same window area where number, com selected. namely, the number, size, when subfile: Display Subfiles be item is TEST80.DAT subfiles Current will This file comments 80 asking menu number of comment is displayed File: Figure E-7: The when alternate window contains in the window 8 be can subfiles as well as listing originally into the datafile recorded. under Figure E-7. This is comments placed was Subfiles Contained Therein. This selection is an the Edit File Comments Menu. The above men action data file in the eight the physiological data when what the of will terminate the window, and restore the APPENDIX E 131 Enter Comment Line Number to <ESC> to complete Comment: a comment lab volunteer Figure E-8: The Edit File Comments then allows editing to proceed. The This is used To enter/modify to alter #8. This the information, is example shown the move is previous a submenu is submenu shown item figure. under comment to highlight the corrections and press to edit, in Figure E-9. 'time-stamp' the cursor to the relates selection contents of <RETURN>. Make the and press quit to to EDIT subject Comments Menu. The resulting submenu (zero) 0 <CTRL-cursor> menu selection queries a comment number Modify Status-Comment the Edit File 4 edit : line. line specific <RETURN> again. When complete, pressing <ESC> will update the file comments window and the parent menu will then be restored to its previous appearance. Note: this procedure was developed to assist in old-version updating datafiles to the original format current datafile format did number of actual physiological signals the acquisition algorithm allowed data which physiological #Chnls: File: # # Originally Recording status Recording line in a Recall that data is integer numeric channel, convert As indicated <ESC> the by format. This present real work, this The datafile to be Time only processed and is the is hh:mm 2 07/19/91 (24Hr) is used then RPW, an to write the 05:34 menu allows action item be used selected this adjustment under of the converted of this list appears constructs data into be interrupted a new by in an a single datafile. pressing the data is necessary in the channels in the datafile. channel through the FPW. A list to be the Main Menu. the data representing the EKG for any specific channel appearance of extract process can conversion of procedure can is displayed in the RPW list. Coincidently, the and in the although versions of Time: xx/xx/xx Date selection procedure voltages, a message key. Note: Date: into the integer datafile in two-dimensional collected it to Later number of channels data files. This Transfer Single Channel. originally Sample Below Modify Status-Comment-#8 The The channels regardless of only that Recorded Channels 'time-stamped' five were present. of recording filename.DAT Original E-9: that needed. of channels was supplied. Original Figure number Status-Comment-#8 Modify infrequently were always recorded the for is thus and include the not Original datafiles recorded. used 'transferred' of available channels is selected in Figure E-4. After from this a selection is APPENDIX E a made, 132 processing the total The file, output (i.e. channel selected EKG: Plot. This to graphically single- display filename9 original Although the is item an action by Analyze/Find-Peaks. The RPW appears processed out of RPW, the name This (EKG: seconds through selected use of and process Plot) is selection maintains the total is deceiving, of a this on indicating the FPW file the the under in the and the graphics be the Main Menu. which subfile is used procedure. use of by Thus the FPW. is currently in the datafile. As indicated by (subfiles) procedure can file through the real voltage a counter be interrupted item an action number of subfiles can new procedure and use of described Transfer Single Channel above for the filename procedure prompts a based the Main Menu. This under in the the first 20 eighth point file. The filename is the assigned .PI). every item menu created processed out of a new extension and image is automatically displayed. Discussion menus is deferred until Section E.5.1 (page 135). for any datafile being is automatically file, voltage graphics environment the or selection channel real voltage resulting real using the .EKG is currently which subfile in the datafile. termed the (filename) specification used line indicates status number of subfiles being a message pressing the <ESC> key. Upon in procedure display is automatically restored. At this point, the STATUS Window indicates EKG peak detection is completed by changing the ekg peaks status completion, the Main Menu 'NO' from to 'YES'. IHR: Plot (time). tion combines neous heart two distinct rate (IHR) is procedures activated the ihr status is checked prior IHR: Patch/Plot. This lection two distinct also 2.4.2) combines Since the IHR.Patch dataset (R-R intervals), the total status ing into one. item The under the Main Menu. This to procedure immediately by status is peaks status the is compute selec the instanta to graphically procedure modified accordingly. checked prior As to computing the IHR to plotting the IHR dataset. selection the instantaneous heart procedure. Upon an action followed to in Section E.2. 2, the ekg referred tion is selection the resulting dataset (Plot. IHR. T). The ihr display and This is an procedures rate is item action into activated procedure one. The followed involves number of points the Main Menu. under procedure to Patch immediately by removal removed of points This se (Sec the Plot. IHR. T from the IHR is displayed in the RPW. termination, the Main Menu display is restored. The ihr. patch accordingly. As above, ekg peaks status is checked prior to patch normal procedure is and modified re- computation of the IHR and the ihr status is checked prior to the plotting procedure. 9Speaking filename and DOS concerning file specifications, in 'typ' portion is the extension. the a file named 'myfile.typ', the 'myfile' portion is the APPENDIX E 133 IHR: Parse. was not This is selection an described in Section 2.4.2 may be The Parse routine before used under allows graphical it to inspection replace the Main Menu. the processing methodology when or after application of routine10 of a contiguous portion of item action of the Patching key, which the controls mention made 'step-size' taken here when a concerns are covered. and possible extraction useful included the function is key cursor just in removal removal of glitches Parsing described. The only selection detailed. This procedure the IHR dataset linear trend existing in a portion of the IHR dataset or 'end' are near either of the IHR dataset. The instructions for operation of the environment so are not was the existing IHR dataset. This is of a This pressed. if they on-screen and of the <PgUp> After pressing be one dataset- <PgUp>, if the next key pressed is a cursor key, then each 'step' will point in size. To increase the number of points in a 'step' to say 10 dataset-points, <PgUp> followed by the '1' '0' and keys the at top of the keyboard, then press press a cursor key. When completed, the routine re-computes the IHR dataset IHR dataset concurrently in a split graphics window. The ihr if it had been not re-computation of HRV: Plot (normal). selection combines rate variability display This (HRV) the resulting is and progress of accordingly. selection an action into procedures followed item The one. under is set to the Main Menu. procedure immediately by dataset (Plot. HRV). Since this stage the to compute a procedure This the heart to graphically involves the interpolation from status an is checked prior to computing the HRV and the hrv status to plotting the HRV dataset. PSD: Plot/smth (auto-fit). This status new 'YES' R-R interval function (Section 2.1), the RPW appears the interpolation is indicated by a message. The hrv status is modified The ihr checked prior is selection activated R-R interval dataset to an is and two distinct displays the The ekg peaks status is checked prior to parsing and the ihr status is checked prior to the plotting procedure. previously. the IHR and combines This several selection distinct is an action procedures into item one. under The the Main Menu. procedures included are: 1. Apply a Hanning window 2. Blackman filter this new to the HRV dataset at 3. Compute the fast Fourier transform 4. Calculate the power spectral 5. Calculate the PSD 10 In ASYST, this dataset; five of hertz; this dataset; density (PSD); powers and ratios as routine uses a restricted form of defined by the current the GRAPHICS. READOUT parameters; and, system word. APPENDIX E 134 6. Plot the resulting PSD dataset out to a frequency set by the (indicated in the STATUS window on the Main Menu display). freq plot value The smooth, window, psd, and psd. power status indicators are modified accord ingly. The hrv status is checked prior to application of Blackman filter, the Hanning window, and the PSD The calculation. is psd status to plotting the HRV checked prior dataset. PSD: Plot/smth (user-fit). This selection performs Menu item erator is exactly the with one exception. prompted useful when for the producing This is selection same an action functions graphs which are used the Main Menu. under the PSD: Plot/smth as the plotting During of to be maximum y-axis value item the resulting PSD dataset, the op This feature is extremely plotted. to visually Main (auto-fit) compare relative spectral power amplitudes. Process Respiration Data. This procedure window second This data window processed from the is then this above) extracted the original dataset from the datafile, REPORT: Print Cover Page Data. Menu. This the about This procedure produces and sends analysis process. cessing parameters, and The dataset comments selection to the in the status is the bounds and must be of a entered. is (same set accordingly. Since datafile, be need an action printer a report item in the characteristics are reproduced checked. under the Main containing information important all of obtained indicators no status and dataset is density respira. the integer data file of for the Main Menu. dataset for determination respiration The under appears are prompted power spectral graphically. integer item for the filename FPW) respiration displayed and routine uses an action EKG data. The RPW the dominant respiratory frequency. A steps as is selection (through the prompts corresponding to the just 64 This search and pro report made by this Additional information concerning the specified frequency bands is produced includes various items such as: total band power, band power ratios, band peak procedure. and amplitude ratios in Appendix D and others as which contains described here. This This tent E.5 The of concludes the heart well. the procedure checks the rate the default operating example of program output the variability the form report from the produced normal analysis psd. powers status normal steps of analysis necessary to during obtain is shown procedure its operation. the frequency con of some studied subject. Additional Features general An procedures of the Program described above are sufficient program parameters without graphical output in for an analysis hardcopy using form. There all are APPENDIX E the default ing features incorporated into the additional many graphical E.5.1 In 135 program and plots, the graphical inferred that the occupy the are half data, top half of processed area an operator storage and retrieval of processed DOS file simple is the full output generated additional here they are. First of all, there so implementing assist data, in alter combining management commands. Graphics Environment Menus describing was parameters, to program two types the were available while of plot areas screen and full that can screen areas. display (TOP) screen area the desired plotting features for the EKG: Plot Main Menu selection, it in the be for used The half graphics environment, display graphical screen plot areas of simply the bottom half (BOT). The default plotting or (FUL). The default to plot area can be superceded by selecting This selection can invoking be done directly from the Main Menu by selecting one of the the two PLOT AREA: menu items. The first item in the STATUS list, cur. graph, indicates what the current plot area is. Upon is set its default All of analysis menu return located environment previous the procedure. to the Main Menu from any Main Menu selection, the value plot at used the lower left located in the are upper portion of of graphics from accessible one of the plot left right area of of the display screen with display and an options the the display. available is or in to which create upon normal (or the options The Multigraph Menu is the from the Main Menu 80% portion environments The GRAPHING Menu is sections. current plot (FUL). areas two type are own menu. directly the graphing information displayed in the There its the area prior respiration graphs, each entry into the with graphics procedure) described in environment and it is second graphical available as a submenu selection item from GRAPHING Menu. GRAPHING Put Comment Print Graph Multi-Graph Set Max <ESC> Figure E-10: The GRAPHING hard copy, frequency comment insertion, plotted can also be menu allows and Freq to Exit various options entry into the Multigraph changed for spectral plots. for plotted graphs: environment. The printer maximum APPENDIX E 136 GRAPHING Menu. items including EXIT an The GRAPHING Menu, in Figure shown Put Comment. This selection is a submenu item Menu environment. The appearance of the submenu is This submenu allows the creation of two in Figure E-ll. (0.0-1.0 )in the the the center of Erase.Label Orientation: values to ninety (90). Character: fields to and Apply Label 1 Label 2 Locate X a Locate Y Erase_Label_l Apply.Label.2 Erase.Label.2 TOP FULL two environment. portion of the This "Label: printer environment. controls This system, Label: replaced direction entered is The by selected 0 Character : updates the is an the prints selection is 0 in degrees. to EXIT <ESC> allows creation Menu, generation The plots the GRAPHING current menu a submenu any under from the lower information in the display to printing to the Multigraph generated. the the resulting appearance of it is item action analysis verified prior of comment FUL : from the GRAPHING Menu procedure removes This orientation of each character as coordinate can labels. selection display, display, and Multi-Graph. ING Menu is Menu, the the presence of Menu (0). by setting both the be formed by setting Graph Label Current separate graph Print Graph. portion of zero other values11. BOTTOM Figure E-ll: The Put Comment and placement of left to obtained .9500 Apply.Label.1 Menu Character:) and Unique labels Orientation: .5000 current plot area can by normalized coordinates improperly can be removed horizontal orientation are obtained by setting both of the Orientation: values (Label: Labels in a vertical orientation (facing right) are the Label: placed which are placed Labels in selections. may be the label is defined Labels plot area. which menu to the Main Menu. the GRAPHING any location in the current plot area. Note that the also be selected from this submenu. of four under labels separate offers shown at The location E-10, option which will return program control ... under The the GRAPHING unaltered and which printer. left avoid a runtime error. item is to the upper is shown from the Locate: the GRAPH in Figure E-12. position. values represent angular units Character: in controls a standard polar APPENDIX E 137 Multigraph TOP BOT IHR.T HRV (orig.) PSD RESP IHR. I HRV (smth/w) Vuport Figure E-12: The MultiGraph the menu allows This The the menu but the menu. To graph placement of two active vuport (plot area) is always can create a to plot be by changed select multigraph, (i.e. in that PSD) select another graph type (i.e. GRAPHING Menu, Print Graph run vuport. maximum E.5. 2 data on Apply at display Then of the of in the labels, Comment the select the BOT select top specific vuport To second vuport. press con the bottom and obtain <ESC> to return to procedure and then invoke the is a submenu submenu generated Search/ Program Parms frequency to plot out selection submenu at to item when under the GRAPHING from the Main Menu and this point allows graphically when is detailed in Sec displaying changing the PSD RESPiration datasets. little thought, through the some use of interesting both graphing plot combinations and environments labelling can be accom just described. Supplemental Program Utilities With the can a indicated an alternate vuport at plot descriptive tion E.5. 2 (page 139). Access to this and/or to the plot areas on say, the TOP vuport, then selection The is the identical selecting the SET: plished graphs of processed procedure. Set Plot Freq. This Menu. the selecting RESP) a printout of a multigraph with With two of the environment allows currently. the plotting display. same the BOT : graphics utilities now commence by describing discussed, coverage of the the remaining individual supplemental program utilities menu selections from the Main Menu. File Editor/DOS Utilities. This portion of the menu item This covers selection the DOS is a submenu utilities that item under were not the Main Menu. discussed previously. APPENDIX E 138 Referring to Figure E-5 (page 128), these DOS utilities include DIRectory fist, DELete file, COPY file, and REName file. D: This Directory Utilities Menu. This directory filename, used as resulting display the is filename' can shown * * . be DISK SPACE INFORMATION * * 9.06'/. 90 947. Total 21 ,204,992 100.00*/. : Move with <DIR> 08/02/91 08/02/91 7839 08/02/91 THET14A.PRG 3523 08/02/91 THET15A.PRG 3599 08/02/91 THET16A.PRG 2109 08/02/91 THET17A.PRG 6317 08/02/91 THET18A.PRG 6006 08/02/91 Directory Display the files requested This This allows for the selection is procedure available listing by an action produces a a space on a quit pected and allows item under small the File Editor/DOS window (not shown) and the target filename. The <RETURN> pressing <ESC>. If from the procedure, because of Utilities Menu. This used for file no filenames nature of selection procedure renaming. are entered and an error message will the operating Rename_File. This but is drive scrolling feature. for the copy source filename and The must be pressed after the entering each filename. by <PgDn> 03:13p 03:13p 12:24p 12:37p 12:26p 12:27p 12:27p 12:28p 12:29p lists the prompts voked ft <PgUp> \USERPROG\ASYST\ JUNK4 08/02/91 -File. The . <DIR> Utilities Menu. same * ,283,968 2441 to (C:) ,921,024 THET13A.PRG Figure E-13: The invoke the search parameter. 1 THET12A.PRG key the 19 C . Copy used as Directory Listing of examination of selections Used EXIT Directory Directory in Figure E-13. Available to three Editor/ DOS being the default drive specification passed directory command (DIR), the current default search parameter. Also, a specific path, specific 'wildcard * <ESC> other the File under commands: Just like the DOS routine. or a the and item an action following the only difference procedure with to the FPW is selection the is the an action functions procedure <ESC> is is in pressed be displayed. This is ex procedure. item identically under as the File Editor/DOS the Copy.File procedure APPENDIX E 139 Delete_File. This Utilities Menu. This the FPW. The the and file or not. the file, As found file(s) operator a is selection an action procedure prompts by the delete is queried, for feature, safety a response of 'Y' is for each a item filename to be deleted through displayed in the RPW procedure are file the File Editor/DOS under found, as to simply pressing <RETURN> sufficient will not delete required. REPORT: Print Band Data/Ratios. This selection is an Main Menu. The first of the REPORT: menu items, described gives to delete the whether data concerning the results the of analysis item action on page under 134, normally detailed However, process. the information concerning the frequency bands and other seldom used ratio computations can be generated. This procedure produces a report form with this additional information it to the and sends to printer hardcopy. produce a REPORT: Print Band Data/Ratios. This Main Menu. This procedure produces exactly the the REPORT: Print Band Data/Ratios directs the STORE Data to File. of processing eliminate processed these The FPW is already the data This during data special storage to used at a item action form files, under is an action item under to the operator to file. data This or new storage enter another file. Entry filename graphs are procedure creates of a since The time12. To important data into it for later and stores all name of storage selection the Main Menu. some additional a special the just described for as The only difference is that this display for runtime review. later date if are stored the an a normal analysis requires a certain amount of the enter exists will require is selection. video selection re-processing the data needed, the one of to the generated report selection same report retrieval. filename which duplicate filenames filename is required, use the Delete.File option from the File Editor/ DOS Utilities selection from the Main Menu to delete the existing file. Upon are not If the allowed. procedure completion, same program control This RECALL Data from File. This procedure retrieves memory in the processing. data stored proper variables. Upon procedure to appearance of access and change i2The R-wave peak the is selection in a storage completion, this returned This data SET: Search/Program Parms. Menu. The is is shown process alone requires item and places becomes selection search parameters used detection action program control This submenu an file now to the Main Menu. is the data in the for available is the Main Menu. under returned a submenu to the Main Menu. item in Figure E-14. This for the R-wave approximately 5-6 peak computer's subsequent post under submenu detection minutes the Main to is used procedure. perform. APPENDIX E 140 PROGRAM ft PEAK DETECTION PARAMETERS Voltage Threshold: .9500 Index Threshold: 256 IHR Patch 20.0000 '/, Band: Smooth Cutoff Freq. 5.0000 PSD 1.0000 max Plot Freq. Figure E-14: The Set Search Parameters data during All quantities set the PSD To 95 : Scan Window Size Options: 1024 gives 59 BPM maximum 512 gives 117 BPM maximum 256 gives 234 BPM maximum 128 gives 468 BPM maximum window allows adjustment of several parameters processing. by this Plot Freq. max 256 to EXIT MENU <ESC> used Scan Window Size: Zoom Window Size menu13 were referred item, which was just to in Sections 2.4.1 through 2.4.3 to in referred Section E.5.1 except 137. on page for any of these quantities, highlight the selection and press <RETURN>, this highlights the value itself. Enter the new value and press <RETURN> again. this enter new Exiting Note: this be menu can values menu returns program control through the Main Menu accessed a generated report will contain changed after data processing, the will not correspond are also printed the in the appearance of new values will to the these about be printed on obtain Remember that parent menu. as well as information actual parameters used the final GRAPHING Menu. quantities. the report. analysis If they are Thus, they which results, report. SET: PSD Ranges/Labels. The to its this menu, This after selection the Set is item an action Frequency the Main Menu. under Band Edges menu item has been for frequency band #3, is shown in Figure E-15. The bounds of the specific frequency bands, discussed in Section 2.4.3, are pre-set to the bands normally studied. However, if new bands or different bands require analysis, the upper and lower frequency limits of these new bands can be set with the use this submenu. Selecting the number of frequency bands desired is done using the first selection (Set Number of Frequency selected Bands 5). Number entry is performed just as for the previous menu item just described (SET: Search/Program Parms). A table on the left side of the display (Defined Frequency Bands) can lists the frequency current bands defined. A maximum of ten frequency bands be defined. Set Frequency Band Edges. This selection is a submenu the PSD Ranges/Labels Menu. After item selection, the for the number of number ure or E-15) l;,The index zero at the to frequency band quit. the lower threshold quantity A right here to be sub-submenu corner was referred of the operator item is under prompted adjusted and must enter a valid will then display to previously as appear and await (shown in fig modifications the temporal proximity threshold. APPENDIX E 141 PSD Defined Frequency 5 Bands are Frequency Band Selection Menu Bands Defined Set Number All Frequencies in Hertz Band Band Lower Upper # Name Edge Edge Set of Frequency Frequency Bands 5 Band Edges Set User Band-Ratios Exit to System 1 VLFP .0100 2 MLFP .0400 .0700 3 LFP .0100 .1500 4 HFP 15-50 .1500 .5000 5 HFP 15-100 .1500 .0400 Change 1.0000 Frequency Band Number: Band Name: Lower Edge: Upper Edge: 11 SPECTRUM .0124 25.3924 Figure E-15: The Set Search Parameters used during data processing. Band Menu 3 LFP .0100 .1500 Exit to Main Menu window allows adjustment of several parameters APPENDIX E to the 142 listed. quantities Data is menu returns program control Bands table is the updated with entered as to the relate to each The default other, as the PLOT AREA: Top. band This PLOT AREA: Bottom. the Section E.5.1 on edges are Full on channel routine can be to its selection This This is selection used in This place of frequency bands. is originally compiled These default an action is is ratio quantities Exiting this menu 135) for item the Plot All Channels ... item. under this the Main Menu. See menu item. the Main Menu. See the under this use of an action menu item use of item the Main Menu. See the under this an action 136) for is item use of an action selection for the parent menu. selection Graphic Utilities (page Display. this which adjustable. currently Graphic Utilities (page Create Multigraph. Section E.5.1 of application software. Graphic Utilities (page 135) for on program the time at under to date. would return program control Section E.5.1 the item are calculated analyzed submenu would allow runtime adjust frequency a submenu ratios found in the specific quantities sufficient The intended just 2.4.3, various together to form the final have been to be been implemented not quantities are established when and assembled ratios in Section mentioned Exiting this Defined Frequency above. the and menu, selection was Ranges/ Labels Menu but has As writing. described information. new Set User Band-Ratios. This the PSD parent menu item. the Main Menu. under option under the File This Editor/ DOS Utilities Menu (page 129) to this the is that only one channel can be displayed at a dataset is graphed, not just the first 20 seconds worth. That this procedure and time, and that the procedure also view the collected physiological data. The differences between other mentioned entire displays every eighth point just as the other channel graphing procedures do. The filename is upon entry printer. An of a valid upper about 20 seconds, display) is and procedure mentioned on page (less This under be to graph send some from Modify is an immediately displayed the Status-Comment image to the 'panel' each display a nominal action graphics listed file information in the program control returns selection is Note that placed on one a single channel completion, 131 available procedure panels can display RESHAPE Acquis. File. As is in Figure 15 (page 58). that 5 to option from this shown screens are needed datafile. Upon for through the FPW. The filename. An example output left 2-1/2 prompted represents screen. 256 Thus, almost subfile acquisition to the Main Menu. item #8, under the the Main Menu. original acquisition APPENDIX E datafiles 143 recorded To were supplied. developed to the RPW be together 1, 2 new and and 4. datafile any time A Strangely data even if only two storage requirements the file to be to prompt for channels of physiological for these reduced is prompted which channels to extract. The to actual file The operator has the option data procedure was file than the for through the FPW in ascending order. For example, channels 1-3 datafile is constructed and the operator is the original. files, this valid channels and create a smaller new replace prior the the data for the name of appears channels of reduce extract The original. five and then channels extracted must or 3-5, but asked to not channels to verify that the cancel this procedure replacement. enough, this procedure has found use in subdividing multiple channel ac datafiles into smaller ones which are able to be transported using high density 3.5" diskettes. This is important because a five-channel acquisition file can be as large as 2,623,488 bytes in size, much too large for these 1.44 MB diskettes. quisition Manual IHR: Compute HRV : Compute HRV : Smooth HRV: Window IHR: Plot HRV: Plot PSD: Plot Press Figure E-16: The Manual a vertical space of Processing (index) (smth/wind) (current) to EXIT <ESC> Processing Commands Menu, display additional menu 18 lines to MANUAL: Single Commands. This Menu. As the early mentioned cedure operated continue to in Section level these This procedures also updates selection command specific-procedure single procedures was made. ing E.2, from the ASYST allow a Commands Menu selected is a submenu versions of the item under implementation, STATUS List Menu, has the Main program used single pro line (from key-combinations menu provides access the from the Main items. a menu to these with current actually). offering the procedures. To original Implement processing information. APPENDIX E The 144 this appearance of EXIT to DOS. mentioned the This is operator response of or 'y' EXIT to ASYST. will exit used enter or at to this level the direct the operator of <RETURN> will This of the ASYST complete tion software. and layered the ASYST this prevent program the item an action level, return software that programming not software without program 'GO' at entering the operator designer, PC the program, Only session. Menu items is included on an of a the index the If option command primitives or words can for an operator to primitives usage perchance events place command rate ASY'ST ASYST of me. the ASYST reference, the recommended knowledge to the Main convenience and quick submenu selection of the the Main Menu. This under the operating instructions for the heart For quit return session. functions. It is original and session inadvertent termination to verify the intention to is Although the Main Menu. under to terminate the used selection item action environment and place computer control at guidance of at an respond perform specialized this level in Figure E-16. terminate the This the Main Menu line. It is be will to is line. To command prompted 'Y' shown selection earlier, this item is to the DOS control is menu line and pressing application. variability analysis applica listing of all following pages. the Main Menu Index Starting the program, Stopping [125] the program, The Main GET: Data [125, 144] Menu, left - PSD: Plot/smth (user-fit), [134] REPORT: Print Cover Page Utilities, [128, 137] Plot All Channels (auto-fit), [133] column: Acquisition, [127] File Editor/DOS PSD: Plot/smth 20 sec, REPORT: Print Band Data/Ratios, [139] REPORT: List Band Data/Ratios, [139] EXIT to [129] Data, [134] DOS, [125, 144] Edit File Comments, [129] Comments, [130] Modify Status-Comment-#8, [129] Display File Comments, [130] Display Subfiles Contained Therein, The Main Edit File (value), [139] (value), [139] IHR Patch % Band: (value), [139] Smooth Cutoff Freq. (value), [139] PSD max Plot Freq. (value), [139] Scan Window Size: (value), [139] Zoom Window Size: (value), [139] Index Threshold: SET: PSD Ranges/Labels, [140] of Frequency Bands, [140] Set Frequency Band Edges (value), EKG: Plot, [132] Main Graphing Menu, [136] Put Comment, [136] Print Graph, [136] MultiGraph, [136] Set Max Freq., [137, 139] IHR: Set Number [140] Band Number (value), [140] (value), [140] Lower Edge (value), [140] Upper Edge (value), [140] Set User-Band Ratios, [142] Band Name Analyze/Find-Peaks, [132] (time), [132] PLOT AREA: [132] PLOT AREA: Parse, [133] HRV: Plot Parms, [139] Voltage Threshold: Channel, [131] IHR: Patch/Plot, [139] SET: Search/Program _File, IHR: Plot column: file, [139] STORE Data to File, Directory D:, [138] Directory C:, [138] Directory B:, [138] Directory A:, [138] Copy [138] Rename-File, [138] Delete-File, [139] EKG: right RECALL Data from [131] Transfer Single Menu, Top, [142] Bottom, [142] Create Multigraph, (normal), [133] 145 [142, 136] APPENDIX E 146 TOP, [136] BOT, [136] IHR.T, [136] HRV (orig.), [136] PSD, [136] RESP, [136] IHR.I, [136] HRV (smth/w), [136] Full Channel Display, [142] Process Respiration Data, [134] RESHAPE Acquis. File, [142] MANUAL: Single Commands, [143] Compute, [143, 143] HRV: Compute, [143, 143] HRV: Smooth, [133, 143] HRV: Window, [133, 143] IHR: Plot (index), [133, 143] HRV: Plot (smth/wind), [133, 143] PSD: Plot (current), [143] IHR: EXIT to ASYST, [144]