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FIRST EXPERIENCE WITH SALBUTAMOL - INDUCED CHANGES IN THE PHOTOPLETHYSMOGRAPHIC DIGITAL VOLUME PULSE Aleksandras Laucevičius, Ligita Ryliškytė, Žaneta Petruionienė, Milda Kovaitė, Nerijus Misonis Department of Cardiology, Vilnius University and Vilnius University Santarishkes Hospital, Medical Center "Kardivita" Vilniaus universiteto ir Vilniaus universitetinės ligoninės Santariškių klinikų Kardiologijos klinika, Medicinos centras Kardivita Keywords: photoplethysmographic digital volume pulse, endothelial function, coronary heart disease, arterial hypertension. Summary. Photoplethysmographic digital volume pulse analysis provides an additional possibility to evaluate arterial stiffness and to analyze the reflected pulse waves from the lower part of the body. Systemic effect of beta2-adrenergic agonist salbutamol is partially mediated through the L-arginine-NO pathway. Attenuation of photoplethysmographic digital volume pulse parameters under salbutamol inhalation could be a means of evaluating vasomotor endothelial dysfunction in cardiovascular patients. The aim of the present study was to estimate the digital volume pulse parameters after the inhalation of salbutamol in patients with arterial hypertension, coronary heart disease and to compare them with the results obtained in healthy adults. Normal response of digital volume pulse to salbutamol in healthy subjects was a decreased height of the inflection point (IP) and the prolongation of peak - to -peak time (PPT). In groups of patients with arterial hypertension and coronary heart disease the typical response was attenuation in the drop of the height of the inflection point and the corresponding minimal or absent prolongation of the PPT interval. The blunted response of photoplethysmographic digital volume pulse parameters to inhaled salbutamol in hypertensive and coronary patients could suggest a disturbed endothelial vasomotor function in these patients. Seminars in Cardiology. 2002; 8(1):87-93 Salbutamolio sukelti fotopletizmografinio digitalinio turinio pulso pakitimai: pirmoji patirtis Raktažodžiai: fotopletizmografinis digitalinis tūrinis pulsas, endotelio funkcija, koronarine sirdies liga, arterine hipertenzija. Reziume. Fotopletizmografinio digitalinio turinio pulso analizė suteikia papildomą. galimybę jvertinti arterijų standumą bei isanalizuoti pulsines bangas, atspindėtas is apatinės kūno dalies. Sisteminis beta2adrenerginio agonisto salbutamolio poveikis yra dalinai medijuojamas per L-arginino NO kelia.. Fotopletizmografinio digitalinio pulso parametrq kitimas po salbutamolio inhaliacijos gali būti kardiovaskulinių pacientų vazomotorinės endotelio disfunkcijos jvertinimo būdas. Šios studijos tikslas buvo jvertinti digitalinio turinio pulso parametrus po salbutamolio inhaliacijos pacientams, sergantiems arterine hipertenzija, koronarine sirdies liga, ir palyginti juos su sveikq suaugusiųjų. rezultatais. Normalus sveikq asmenij digitalinio turinio pulso atsakas j salbutamolj buvo linkio tasko aukscio sumažėjimas ir intervalo tarp viršūnių prailgejimas. Pacientų, sergančių arterine hipertenzija ir koronarine sirdies liga grupėse tipingas atsakas buvo mažesnis linkio tasko auksčio kritimas ir tai atitinkantis minimalus intervalo tarp virsuniq prailgejimas. Fotopletizmografinio digitalinio turinio pulso susilpnėjęs atsakas i jkvėptą sulbutamolj sergantiems hipertenzija ar koronarine sirdies liga pacientams leidžia jtarti sutrikusią vazomotorinę šių pacientų endotelio funkcija. Kardiologijos seminarai. 2002; 8(1):87-93 Photoplethysmography (PPG) - non invasive technique where non-visible infrared light is emitted into the skin. PPG device should measure the volume by optical methods. Light may be transmitted through a capillary bed such as is found in the ear lobe or finger tip. As arterial pulsations fill the capillary bed, the changes in the volume of the blood vessels modify the absorption, reflection and scattering of the light. Depending on the blood volume in the skin, more or less light is absorbed. By measuring the non-absorbed light, the changes in the blood volume can be measured [1]. Transmission of the infrared light through the finger and its photoplethysmographic measurement gives a digital volume pulse (DVP) [2]. The DVP exhibits a systolic and diastolic components "a" and "b", characteristic "notch" or point of inflection (IP) in its downslope and the time interval between the first (systolic) and second (diastolic) peaks of the DVP (AT) [3] (Fig. 1A). The second [2] or the first [3] derivatives are used for estimating the inflection point IP and its changes. The inflection point contributes to the smoothening of the pulsation of the arteries - the so called "windkessel effect" [4,5]. Two features of the arteries - elasticity and peripheral resistance - allow them to smooth out the pulsations. The mechanism is similar to the type of the pump the Germans in the 19th century called windkessel, so the smoothing of the pulsations by the arteries is often called the windkessel effect. It results from the increased compliance of the large arteries and to a decreased venous return to the heart [5]. Pressure pulse waveforms are being studied more extensively than the volume pulse [6]. The decreasing of the pressure wave reflection from the peripheral arteries accompanied by changes in pressure pulse is a typical response to glyceryl trinitrate (GTN) [7]. Changes in the DVP produced by GTN parallel those in the pressure pulse [8]. Recently Chowienczyk et al. [3] proposed studying vascular reactivity and endothelial dysfunction by measuring the systemic effect of beta2-adrenergic agonist salbutamol on the inflection point (IP) of photoplethysmographic digital volume pulse. Vasodilator responses to beta2-adrenoceptor agonists, are mediated in part through the nitric oxide pathway [9,10]. The vasodilating effect of salbutamol on the forearm resistance arteries in humans is partially mediated through the L-arginine-NO pathway [3, 9,10]. This response could be attenuated during the concurrent blockade of NO synthesis . by A/G-monomethyl-L-arginine (LNNMA). The aim of this article was to present our initial experience with the analysis of salbutamol induced changes of photoplethysmographic digital volume wave parameters in patients with arterial hypertension and coronary heart disease and to compare them with the measurements in healthy adults. Methods Study population Fifteen healthy subjects (7 men and 8 women; aged 30.72±6.93 years) with no evidence of arterial hypertension (blood pressure < 140/90 mm Hg), hypercholesterolemia, diabetes mellitus, cardiac or peripheral vascular disease, or any other systemic condition were included in the study. Out of 322 patients participating in the long - time follow-up program in which PPG digital volume pulse assessment was performed 56 patients (21 women and 35 men) with mean age of 53 ±11 years were selected for the present analysis. The patients were divided into two groups - the first group consisted of 26 patients with angiographically proven coronary heart disease and second of 30 patients with primary arterial hypertension. The most relevant characteristics of the coronary and hypertensive patients and control subjects are shown in the Table 1. There was no significant difference between the patient groups with regard to age, but subjects in the control group were younger than the patients of both groups. Blood pressure was significantly higher in the arterial hypertension (AH) group than in the coronary heart disease (CHD) group and subjects in the control group. There was no significant difference of blood pressure in the CHD group and control subjects. Most of the patients in both AH and CHD groups had at least 2 cardio-vascular risk factors. Subjects in the control group were without any cardiovascular risk factors. The coronary heart disease group consisted of 26 patients (9 women and 17 men) with the mean age of 55.35±10.12 years. The mean arterial pressure in this group was 127.35± 17.64 mm Hg; there was no evidence of present or past hypertension in these patients. Coronary heart disease was proven angiographically in these patients. Arterial hypertension group consisted of 30 patients with primary hypertension (12 women and 8 men) with the mean age 51.07±11.56 years. The mean systolic arterial pressure in this group was 144.97±27.20 and diastolic87.27± 14.50 mm Hg and they were significantly higher than in group with the CHD. The blood pressure was defined as an average of 3 sitting blood pressure readings taken after 5 minutes of rest on 3 different occasions during a 3- to 4-week period. Acute coronary events were present in 20 (77%) patients from the CHD group. The lipidogram parameters (total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides) did not differ significantly between the CHD and AH groups but were significantly higher in both patient groups than in the control group (Table 2). Pts with AH, Pts with CHD Control P* p** All pts n=71 group p*** n=30 n=26 n=15 17 7 42 9 8 29 Age 51,07±11,56 55,35±10,12 30,72±6,93 0,15 <0,001 <0,001 BMI 30,26±7,14 28,56±3,67 22,76±2,83 0,27 0,02 Systolic BP 144,97±27,20 127,35± 17,64 121,33±11,66 0,006 0,01 0,32 133,52±23,39 76,35±9,40 73,47±8,06 0,002 0,007 0,36 80,35± 12,97 22 0 Sex male female 18 12 DiastolicBP 87,27±14,50 >2 risk factors 24 Table 1 . Clinical characteristics of patient groups (AH and patients CHD patients) and control subjects. 48,34± 13,75 0,03 28,05±5,99 46 p* - comparing AH and CHD groups p** - comparing AH and control groups p***. comparing CHD and control groups Pts with AH, n=30 Total Cholest. 6,98 ±1 ,96 LDL-Ch 4,41 ±1,58 HDL-Ch 1,37±0,38 TG 2,72±2,22 Pts with CHD Control group n=26 n=15 6,48±1,46 5,47±0,97 4,18±1,71 3,12±0,87 1,19±0,34 1,45±1,05 2,13±1,16 1,8±0,74 Table 2. Level of lipids in patients groups (AH and CHD groups) and in control subjects group. p* p*** 0,15 <0,05 0,66 <0,05 0,11 <0,05 0,28 <0,05 p** <0,01 <0,05 <0,05 <0,01 All pts n=71 6,75±1,74 4,28 ±1,63 1,29±0,37 2,42 ±1,76 p* - comparing AH and CHD groups p** - comparing AH and control groups p*** - comparing CHD and control groups All AH and CHD patients were taking antihypertensive or vasodilating medication at the time of their investigation but never tissue ACE inhibitors, third generation calcium antagonists or statins that could significantly influence the endothelial function. The study was approved by the local institution ethics committee. Protocol. All studies were performed in a quiet room with a temperature controlled (25 ± 1°C). All participants were asked to refrain from drinking alcohol or beverages containing coffeine and from smoking for at least 24 hours before studies. They were studied in the morning after overnight fasting. A portable photoplethysmograph Micro Medical MP2000 (Gillingham, Kent, United Kingdom) was used for digital volume pulse analysis. The assessment was performed using the protocol of Chowienczyk et al [3], which was modified by us. Data were collected with the patient sitting in a specially designed arm-chair with the hands comfortably placed slightly below the level of the heart with out stretched legs. The measurements were started after the calmdown period of 20 minutes. The probe was placed on the index finger of the right hand. In the cases when the finger was cold, steady additional warming was applied and only in the absence of peripheral vasoconstriction the measurements were started. Three baseline 30 seconds recordings were carried out at 5 minute interval and then the results were averaged and presented as the mean basal parameter of the digital volume pulse. Three parallel blood pressure measurements were performed using the advanced oscillometric automatic digital blood pressure monitor UA-767 (A&D Company, Limited) during the baseline recordings, the results were averaged and presented as the mean value. Salbutamol (Ventolin Inhaler, GlaxoWelcome) was given by inhalation using the spacer device (four doses of 100mg each). Every dose was inhaled by two deep breaths in from the spacer. Repeated 30 seconds recordings of the PPG digital volume pulse were performed at 5,10,15, 20, 25, 40 and 60 minutes after the inhalation of Salbutamol (SLBTM). The data were averaged by the unit and several mean parameters were calculated (Fig. 1A): IP - inflection point - defined as the relative height of the inflection point expressed as a percentage of the ratio between the amplitudes of two waves: systolic forward (a) and reflected (b): IP=b/ax100% The second point, or inflection point, is thought to be due to a reflection of the aortic pressure wave from the lower part of the body. The height of the reflected pulse is proportional to the amount of reflection from the lower body, which is inversely proportional to the dilatation of the peripheral arteries. PPT - peak -to- peak time - measured between the waveform peak "a" and the point of inflection "b". PPT is inversely proportional to the arterial stiffness. SI - stiffness index - defined as the patient's height divided by the PPT with units of meters per second. Several additional derivative parameters were calculated: A IPmax normalized for corresponding APPT (Alpmax X 10/APPT) APPTmax normalized for corresponding AlP (AIPX 10/ A PPTmax) A IPmax normalized for PPTmax (Alpmax X10/APPTmax) IR PPT and SI parameters after salbutamol inhalation are presented as a mean of the measurements after 10, 15 and 20 minutes (modified protocol) and as a mean after 15 and 20 minutes (original protocol). Maximal IP and maximal PPT were selected from the all recordings: at 10, 15, 20, 25, 40 and 60 minutes after salbutamol inhalation. The basal measurements were compared with those achieved after salbutamol inhalation. Typical response of DVP to inhaled SLBTM in healthy adult is presented in Rg.1B Statistical Analysis. Statistical analysis was performed using the GB-Stat V7.0 for Windows (Dynamic Microsystems, Inc). All measurements are presented as the mean ± standard deviation. Differences between the 2 groups were estimated by the unpaired Student's t test; correlation matrix was used searching for correlations between changes of parameters. All calculated probability values are 2-tailed, and P<0.05was considered to indicate statistical significance. Results. Photoplethysmographic digital volume parameters in all three studied groups before and after salbutamol inhalation are presented in table 3. The typical normal response to salbutamol inhalation showed a drop in the height of inflection point and prolongation of corresponding PPT (Fig. 1B, Fig. 2). The typical blunted response of DVP to inhaled salbutamol consists of attenuated decrease in the height of the inflection point with the absence or only a minimal prolongation of the corresponding PPT (Fig. 3). A decrease in the height of the A IP after inhaled SLBTML was attenuated in most of the patients of the AH and CHD groups compared with normal sinking response observed in the control group although this tendency did not reach statistical significance in the present study. The changes in PPT parameters after inhaled SLBTML significantly differed in both groups (AH and CHD) of patients of the control group. The mean A PPT at 10, 15, 20 min after SLBTM was significantly shorter in the AH group than in the control group; the same tendency was seen in the CHD group but it did not reach statistical significance. The mean APPT at 15, 20 min after SLBTM was found to be significantly shorter in both CHD and AH groups than in the control group. The maximal PPT was also significantly shorter both in AH and CHD groups compared with the control group. The mean Asi at 10,15, 20 PPG DVP parameters Pts with Pts with CHD Control group P* p** p*** All pts (AH and AH, CHD) n=30 n=26 n=15 4,82±6,28 4,82± 10,09 10,24± 13,97 0,99 0,17 0,22 5,97+9,84 4,76±7,23 4,44±10,91 11,31±14,36 0,90 0,11 0,14 6,03± 10,63 9,07±44,91 16,89±40,60 45,91+48,98 0,50 0,03 0,07 19,27±45,86 5,41 ±37,49 15,49±47,77 48,97+51,10 0,39 0,01 0,04 18,30±46,85 0,45±1,88 0,57±3,71 2,29±2,84 0,88 0,04 0,12 0,86+2,92 0,56±1,97 0,87±2,27 2,05±2,94 0,59 0,11 0,22 0,97±2,33 Maximal A IPt 9,66±6,79 10,73± 10,29 18,24± 16,42 0,66 0,09 0,13 11,86±11,05 Maximal A PPTt 37,19±47,71 55,81 ±56,41 110,14+83,01 0,19 0,006 0,04 59,42 + 65,00 Maximal Asit 2,00±2,22 3,92±3,58 0,24 0,07 0,22 2,65+2,52 AlPmax normalized for 1,15±10,21 2,84±3,64 2,98±5,37 0,41 0,44 0,93 2,16+7,38 Mean AlPatIO, 15, n=71 20 min after SLBTM Mean AlPat 15, 20 min after SLBTM Mean APPT at 10, 15, 20 min after SLBTM Mean APPTat 15, 20 min after SLBTM Mean Asiatic, 15, 20 min after SLBTM Mean Asian 5, 20 min after SLBTM corresponding APPT ( AlPmax X 10/APPT) 2, 67 ±1,87 A PPTmax normalized for 0,71 ±3,29 2,10±3,50 1,64+1,73 0,14 0,24 0,57 1,42+3,14 2,69±3,42 0,23±0,16 0,14 0,07 0,001 1,61+3,06 correspondingAlP (AlPXIO/ A PPTmax) A IPmax normalized for 1,34±3,23 A PPTmax ( AlPmax X10/ A PPTmax) Table 3. Photoplethysmographic DVP parameters in patients (AH and CHD) and in the control subject groups. p* - comparing AH and CHD groups p** - comparing AH and control groups p*** - comparing CHD and control groups t - maximal valves measured at 10, 15, 20, 25, 40, 60 min. min after SLBTM was found to be significantly smaller in the AH group and had the same tendency in the CHD group although it did not reach statistical significance. The derivative parameter AlPmax normalized for A PPTmax was bigger in both groups of the patients compared with the control group but reached statistical significance only in the CHD group. The inhalation of salbutamol in doses used had no accompanying alteration of the heart rate or the mean blood pressure. We explored the possible influence of the heart rate upon PPG DVP parameters after the inhalation of SLBTM (Table 4). Parameters R P value (correlation coefficient Mean A IP at 10, 15, 20 min after SLBTM 0,303 <0,05 Mean AIP at 1 5, 20 min after SLBTM 0,241 n.s. Mean APPT at 10, 15, 20 min after SLBTM -0,155 n.s. Mean APPT at 15, 20 min after SLBTM -0,213 n.s. Mean ASI at 10, 15, 20 min after SLBTM 0,203 n.s. Mean ASI at 1 5, 20 min after SLBTM 0,168 n.s. Maximal A IP 0,305 <0,05 Maximal A PPT -0,204 n.s. Maximal ASI 0,197 n.s. AlPmax normalized for corresponding A PPT (A IPmax X TO/ -0,059 n.s. APPT)) A PPTmax normalized for corresponding A IP (A IPX 10/ APPTmax) 0,142 n.s. AlPmax normalized for A PPTmax ( AlPmaxXIO'/ APPTmax) 0,116 n.s. Table 4. Correlation coefficients between changes of IP, PPT, SI parameters and heart rate occurring after salbutamol inhalation. Only the mean A IP at 10, 15 and 20 minutes after SLBTM (r=0,303) and maximal the A IP (r=0,305) after the SLBTML statistically significantly correlated with the changes in the heart rate. There was no significant connection between the changing heart rate and PPT parameters after the inhalation of salbutamol. We investigated the cumulative rate of time when a maximal decrease in the inflection point - A Ipmax was present in order to find out how long after the inhaled SLBTM measurements must be performed. When this time interval was only 15 minutes, the cumulative rate of the decrease in A IPmax was only 41%; it increased to 86 % when the period was prolonged to 25 min (Table 5). The same tendencies were found after the cumulative rate of maximal PPT prolongation analysis was performed (Table 6). Time Cumulative Cumulative Frequency % interval (min.) of pts) (number (number of pts) 5 8 8 14.2857 10 7 15 26.7857 15 8 23 41.0714 20 14 37 66.0714 25 11 48 85.7143 40 6 54 96.4286 60 2 56 100 Table 5. Cumulative Frequency of distribution of the A IPmax decrease time. Interval Cumulative (min.) % 5 3 10 10 15 18 20 32 Frequency (number of pts) Cumulative (number of pts) 3 5,3571 7 17,8571 8 32,1429 14 57,1429 25 43 11 76,7857 40 52 9 92,8571 60 56 4 100 Table 6. Cumulative rate of maximal prolongation of PPT interval. On the basis of these results, we recommend to measure DVP response to salbutamol inhalation after 15, 20 and 25 minutes and to monitor DVP parameters after 40 and 60 minutes in order to observe returning to the baseline of DVP parameters. Discussion. The currently accepted method forthe noninvasive clinical assessing of the vasomotor endothelial function based on the analysis of the flow - mediated vasodilatation in the brachial artery [12]. The reason it can not be used very widely is the necessity of a sophisticated, expensive ultrasound unit and special skills of the investigator [13]. Therefore, wide application noninvasive methods used for the assessment of the endothelial vasomotor function are required. One of the attempts could be the method proposed by Chowienczyk et al in 1999 [3]. They demonstrated that beta2 - adrenergic agonist albuterol (salbutamol) in partly reduces the wave reflection by the activation of the L-arginine - NO pathway and suggested that photoplethysmographic digital volume pulse analysis combined with provocative administration of albuterol might be used for noninvasive assessment of endothelial function. Adrenergic-mediated vasodilation involves a combination of endothelial and smooth muscle mechanisms because salbutamol induces direct smooth muscle relaxation and NO release from endothelial cells [9,10]. The method was applied only to patients with type II diabetes mellitus and revealed a disturbed endothelial function in these patients [3,14]. It is clear from the numerous studies that the endothelial function is disturbed in most patients with coronary heart disease and primary arterial hypertension [15,16]. The main purpose of the present study was to estimate the characteristic influences of inhaled beta2-adrenergic agonist salbutamol on photoplethysmographic digital volume pulse parameters in healthy control subjects, patients with arterial hypertension and coronary heart disease. The normal response of PPG DVP parameters to SLBTM in healthy adult subjects was a distinct decrease in the height of the inflection point with the corresponding prolongation of PPT the interval. In both groups of patients (AH and CHD) the most typical response to inhaled SBTM was a decrease in the height of the inflection point (AlP) with a minimal or absent prolongation of PPT interval. This blunted response of photoplethysmographic digital volume pulse parameters to inhaled salbutamol was found in most the patients with arterial hypertension and coronary heart disease. Statistically different from the values in the control group, the changes in the mean and maximal peak - to - peak time (Mean A PPT and A PPTmax.) parameters- their values were smaller in both AH and CHD groups. The additional parameter - AlPmax normalized forA PPTmax, was found to be significantly elevated in the CHD group patients and its growing almost reached statistical significance in the AH patients in the present study. Attenuated lowering of the height of IP after salbutamol was also present in most of the patients of both groups although did not reach statistical significance in the present study. Changes in PPG DVP parameters after the inhalation of SLBTM, observed in the present study of patients with arterial hypertension and coronary heart disease are in keeping with the results of Chowienczyk et al [3] and Gopaul et al [14] who were able to show similar changes in patients with type II diabetes. Chowienczyk et al [3] showed that the administration of L-NMMA attenuated the salbutamol-induced vasodilation thus proving it to be NO dependent. It was postulated by Chowienczyk et al [3] that A PPT correlates with the delay between the foot of the velocity sonogram at the subclavian vein and that at the aortic bifurcation, i.e. with the time taken for pressure waves to pass from the heart to the site of the reflection and back to the heart. It is comparable with Pulse Transit Time (PTT) obtained during pulse wave analysis - the time the pulse pressure waveform takes to propagate through the length of the arterial tree [3]. It was said that PTT decreases in the stiff arteries in patients with elevated pulse pressure. In our study we could not confirm this proposition. A PPT after inhaled SLBTM did not differ in the group with arterial hypertension, where arterial stiffness was elevated, from the group with coronary heart disease, where arterial elasticity was more preserved. In our opinion, PPT changes after SLBTM go together with a change in the height of the inflection point on the DVP We estimated that the response to SLBTM could not have been contributed to merely heart rate and blood pressure changes. We were not able to discover correlations between the heart rate and A PPT changes under SLBTM. A correlation was revealed (r=0,303, p <0.05) between the heart rate and mean A IP at 10, 15, 20 min after SLBTM. It was shown in the previous studies [3,11] that the blunted response of digital pulse volume and pulse wave parameters to inhaled salbutamol is NO related. Hence we could speculate that the mechanism responsible for the changes in the PPT and IP parameters of photoplethysmographic digital volume pulse under SLBTM found in the present study in patients with arterial hypertension and coronary heart disease could be contributed to a possible endothelial vasomotor dysfunction in these patients. The new technique for noninvasive evaluation of endothelial vasomotor dysfunction must be verified using already available methods. Comparison of SLBTM - induced changes in digital volume pulse with venous occlusion plethysmography coupled with an intra-arterial infusion of acetylcholine revealed a good correlation between both methods in patients with type II diabetes [3,11 ]. The study is under in our institution evaluating the changes in PPG DVP parameters in the groups of patients with and without endothelial vasomotor dysfunction as assessed by the direct infusion of acethylcholine into the coronary artery as well as assessed using the flow - mediated dilatation of the brachial artery on vascular ultrasound images. Several technical details of the study must be discussed. The protocol used in the present study slightly differs from the originally described one by Chowienczyk et al [3]. Data in our study were collected with the patient sitting in a specially designed arm-chair with the hands comfortably placed only slightly below the level of the heart with out stretched legs but not in supine position as was described in the original protocol. The sitting measurements are better because the DVP waveform depends upon the venous return. For the minimization of erratic absorption of inhaled salbutamol the spacer device is used. It was shown by Wilkinson et al [11] that the measured plasma salbutamol concentration is stable between 5 and 20 minutes after inhalation. SLBTM was given in the present study by inhalation using the spacer device (four doses of 10Omg each). We recommended the patient to inhale the dose of SLBTM (1 OOmg) from the spacer two times for more complete appropriation of salbutamol. Repeated 30 seconds recordings of the potoplethysmographic digital volume pulse were performed at 5,10,15, 20, 25, 40 and 60 minutes after the inhalation of SLBTM. Averaging of the measurements was performed at 15, 20 and 25 minutes - the extension of measurements to 25 minutes allowed to increase the cumulative frequency of parameters changes could be seen. Measurements after 40 and 60 minutes were performed in order to demonstrate a return to the baseline of DVP parameters. This was necessary in order to confirm that changes in the parameters are salbutamol - related but not determined by the physiological relaxation of the patient. Among the limitations of the present study must be mentioned a relatively small number of subjects in the control group. Therefore, we could not completely confirm the height of the inflection point as the parameter statistically significantly discriminating patients from control subjects. We also understand that within the groups with arterial hypertension and coronary heart disease there could have been patients with and without endothelial dysfunction and this might weaked the statistical significance of the results. Conclusions. In conclusion, the present study has demonstrates that patients with essential hypertension and coronary heart disease have blunt response to inhaled salbutamol with attenuation of the drop in the inflection point and the minimal or absent prolongation of the corresponding peak - to - peak time on the photoplethysmographic digital volume pulse. Hence, taken in conjunction with the results of the previous investigations, the present study findings suggest that the impaired vasomotor endothelial function could be responsible for a blunted responsiveness of digital volume pulse parameters to salbutamol in hypertensive and coronary patients. References 1. Lund L. 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