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LABORATORY INVESTIGATION VENTRICULAR PERFORMANCE Diminished stroke volume during inspiration: a reverse thoracic pump CRAIG 0. OLSEN, M.D., GEORGE S. TYSON, M.D., GEORGE W. MAIER, M.D., JAMES W. DAVIS, M.S., AND J. ScoTT RANKIN, M.D. ABSTRACT In 12 conscious dogs, a three-dimensional array of pulse-transit ultrasonic transducers used to measure left ventricular anterior-posterior minor, septal-free wall minor, and basal-apical major diameters. Matched micromanometers measured left ventricular, right ventricular, and intrapleural pressures. Electromagnetic ascending aortic blood flow and right ventricular transverse diameter were measured in five of the dogs. A major cause of the inspiratory decline in stroke volume in this preparation appeared to be reflex tachycardia and autonomic changes associated with inspiration. However, when heart rate was controlled by atrial pacing or pharmacologic autonomic attenuation (propranolol and atropine), stroke volume still decreased around 10%, with an inspiratory decrease in pleural pressure of 10 mm Hg. Based on the measurements of ventricular dimension, venous return to the right ventricle appeared to be augmented significantly during inspiration and the transient increase in right ventricular volume was associated with leftward interventricular septal shifting and altered diastolic left ventricular geometry. However, left ventricular end-diastolic volume was changed minimally, implying that alterations in preload were not important. Moreover, transmural left ventricular ejection pressure, calculated as intracavitary minus pleural pressure, was not significantly changed, and it seemed that neither pressure nor geometric components of afterload were altered significantly by inspiration. The inspiratory fall in left ventricular stroke volume correlated best with the decline in intracavitary left ventricular ejection pressure referenced to atmospheric pressure. It is hypothesized that during ejection, left ventricular pressure referenced to atmospheric pressure is the hydraulic force effecting stroke volume and that the decline in this effective left ventricular ejection pressure is responsible for the inspiratory fall in stroke volume through a reverse thoracic pump mechanism. Circulation 72, No. 3, 668-679, 1985. was Downloaded from http://circ.ahajournals.org/ by guest on April 29, 2017 THE EFFECTS of respiratory movement on cardiovascular function are numerous and have been the subject of several extensive monographs.' Systematic investigation into these effects dates back to 1751 when Albrecht von Haller noted an inspiratory augmentation in venous return to the right ventricle of the dog and cat.3 Eighteen years earlier Stephen Hales reported his famous series of experiments in the horse and may have been the first to record the inspiratory fall in arterial blood pressure.4 Although Hales did not make the association between inspiration and the periodic fall in the oscillatory pulse pressure of the carotid artery, numerous subsequent investigators have conFrom the Departments of Surgery and Physiology, Duke University Medical Center, Durham. This work was supported by NIH grants 2R01 H 109315-17 and RO I H129436-01, and by research grants from the Whitaker Foundation and the North Carolina Heart Association. Address for correspondence: Craig 0. Olsen, M.D., Box 3492, Duke University Medical Center, Durham, NC 27710. Received April 26, 1985; revision accepted June 20, 1985. Dr. Rankin is a recipient of the John A. Hartford Foundation Fellowship. 668 firmed this phenomenon and have documented an inspiratory decline in left ventricular stroke volume in both experimental animals5-" and man.'2-14 Several hypotheses have been advanced to explain the inspiratory fall in left ventricular stroke volume, including (1) delayed pulmonary venous transit time,7 15. 16 (2) increased pulmonary venous capacitance and diminished left ventricular filling,'7 (3) reduction in left ventricular preload due to leftward interventricular septal shifting,'81' (4) increased left ventricular afterload from altered geometry due to leftward interventricular septal shifting,8 and (5) increased inspiratory left ventricular transmural pressure, which augments afterload.6 20 The present studies were undertaken to investigate the relative importance of these phenomena during spontaneous respiration in a conscious canine preparation. Methods Instrumentation and acquisition of data. Twelve healthy adult mongrel dogs (20 to 32 kg) underwent surgical preparation CIRCULATION LABORATORY INVESTIGATION-VENTRICULAR PERFORMANCE Downloaded from http://circ.ahajournals.org/ by guest on April 29, 2017 for subsequent studies in the conscious state. The method of implantation of instrumentation has been described previously.21 Briefly, in all dogs an array of pulse-transit ultrasonic dimension transducers was used to measure three orthogonal left ventricular dimensions: the anterior-posterior minor, septal-free wall minor, and basal-apical major diameters. All transducers, except the one in the septal position, which was positioned near the right ventricular subendocardial surface, were placed epicardially. Silicone rubber introducers were implanted in the right ventricle, left atrium, and intrapleural space of each dog, as were bipolar atrial pacing electrodes. In five dogs, right ventricular septal-free wall transverse diameter and electromagnetic ascending aortic blood flow were measured as well (figure 1 top left). Seven to 14 days after recovery from the implantation procedure, each dog was studied in the conscious state while resting quietly on its right side. The dimension transducers were coupled directly to a custom-designed sonomicrometer.21 Prewarmed matched micromanometers (PC-350, Millar Instruments, Houston) were passed via the introducers into the mid left and right ventricles and pleural space. Airtight introducer connectors prevented ventricular hemorrhage and pneumothorax. The aortic flow probes were coupled to a sine-wave flowmeter (Statham, M4001, Los Angeles). The performance characteristics of these instruments have been described previously.22 25 Cardiac dimensions, pressures, and aortic blood flow were recorded on magnetic tape for subsequent digital analysis. Data were recorded in each experiment during normal spontaneous respiration and deep spontaneous respiration against inspiratory inflow resistance through a gauze sponge. Heart rate was controlled by atrial pacing at 10 min- l higher than the fastest heart rate observed during the respiratory cycle. In six dogs, after completion of initial studies, the autonomic nervous system was pharmacologically attenuated with intravenous propranolol (1 mg kg- 1) and atropine (2 mg). Data were collected again during normal and deep spontaneous respirations. At the conclusion of all studies, the animals were killed, their hearts were excised, and the volume of the left ventricular muscle mass was calculated as the average of three volume displacements of water in a graduated cylinder. Data analysis. The recorded analog data were filtered once at 50 Hz and digitized at 200 Hz for analysis. Left ventricular transmural pressure was calculated as left ventricular intracavitary pressure minus simultaneous intrapleural pressure. Right ventricular transmural pressure was determined similarly, and interventricular transseptal pressure was computed as left ventricular intracavitary pressure minus right ventricular intracavitary pressure. The first derivative of left ventricular transmural pressure (dP/dt) was calculated from the digitized ventricular pressure waveform with use of a five-point polyorthogonal approximation.25 FIGURE 1. Top left, Preparation used to assess the three-dimensional geometry of the left ventricle. The F b /| anterior-posterior minor (A to P), septal-free wall minor (S to F), and basal-apical (Ba to Ap) major diameters were measured in the conscious dog and fit to a double hemiellipsoidal model. Biventricular and pleural pressures were measured with micromano- meters passed through implanted silicone rubber tubes. In five preparations right ventricular transverse diameters (S to R) and ascending aortic blood flow were measured as well. Top right, Model of left ventricular latitudinal plane geometry of the left ventricular double hemiellipsoidal model to which dimensions were fitted. A, S, P, and F correspond, respectively, to the placement positions of the anterior, septal, posterior, and lateral free wall dimension transducers. b = external anterior-posterior minor diameter; c = septal-free wall minor diameter; Rs = left ventricular septal radius of curvature in the latitudinal plane. Bottom, Postmortem transverse section of myocardium from one dog demonstrating the actual position of the four epicardial and one endocardial dimension transducers. A anterior; S septal; P posterior; F left ventricular lateral free wall; R right ventricular free wall. = Vol. 72, No. 3, September 1985 = 669 OLSEN et al. Results Downloaded from http://circ.ahajournals.org/ by guest on April 29, 2017 Measurements of left ventricular dimension were modeled by a double hemiellipsoidal geometry as described previously.2' External left ventricular volume was calculated as the sum of the two ellipsoidal segments inscribed by ASPA and AFPA from figure 1, top right. Calculation of external left ventricular volume yielded results mathematically equivalent to the formula for a general ellipsoid, (ff/6) a b c. where a is the major diameter, b is the anterior-posterior minor diameter, and c is the septal-free wall minor diameter. Postmortem left ventricular wall volume was subtracted from external left ventricular volume to yield intracavitary left ventricular chamber volume. Aortic blood flow was either measured or derived from the inverted first derivative of left ventricular chamber volume (-dVI/dt). Geometric deformation of the left ventricle was determined including the latitudinal septal and free wall radii of curvature, as well as septal displacement, and regional left ventricular septal and free wall tensions were calculated according to the Laplace relationship, as described previously.2' Comparisons were made between end-diastolic dimensions, chamber volume, regional wall tensions, and measured and calculated pressures at end-expiration and peak inspiration for both normal and deep respirations by an analysis of variance. Similar comparisons were made for end-ejection dimension and volume data from the same cardiac cycles during which enddiastolic data were obtained. In an analogous fashion, peak ejection pressure, aortic blood flow, and calculated tension data were compared at end-expiration and peak inspiration. Linear regression analysis was used to determine the relationship between left ventricular pressures, intrapleural pressures, left ventricular end-diastolic volume, peak aortic blood flow, and left ventricular stroke volumes throughout the respiratory cycle. Unless otherwise specified, all reported data were obtained during control of heart rate by atrial pacing. L V MINOR 60 Representative analog dimension, pressure, and flow data obtained during three deep inspirations without atrial pacing are illustrated in figure 2. A marked inspiratory increase in heart rate was evident. During inspiration, the fall in intrapleural pressure produced a similar decrease in right and left ventricular intracavitary pressures. Stroke shortening decreased in all three left ventricular dimensions. The end-diastolic diameters and volume changed in a variable fashion because of rate-dependent changes in ventricular filling. This resulted in a progressive and significant inspiratory fall in peak aortic blood flow and stroke volume as inspiration progressed (figure 2). Atrial pacing (figure 3) and autonomic blockade (figure 4) ablated the respiratory variation in heart rate. End-diastolic diameters and volume changed minimally, but peak aortic blood flow and stroke volume continued to decline during inspiration. During normal spontaneous respiration, intrapleural pressure decreased from an average of -1.6 + 0.7 mm Hg (mean + SEM) at end-expiration to -6.1 + 0.7 mm Hg at peak inspiration. With deep spontaneous respiration against inspiratory inflow resistance through a gauze sponge, intrapleural pressure decreased from an averNA Thf'AKt\ E.E.. Ei;.t. DIAMETER LV MINOR S-F DIAMETER 60F AACVr%~t\f\ ItKlJVtYr\APvVAt/VJ~AAAA d * LV MAJOR ~V J-4A A A A DIAMETER (mrnm) ktAVAVMIAAAArdArJYMAPAMV b86i: - AORTI WA (mi/sec) P. RIG HT (mmq ;+ 0-t0 PLEURAL ^ i A0' : Hg) ;0 - PRESSURE (mm Hgj) LE f T l'A k' 5R PRRE 5T C nL A R EE P I~~~Hscn FIGURE 2. Typical analog dimension, pressure, and flow data obtained from a conscious dog during three deep spontaneous respirations without atrial pacing and demonstrating the marked respiratory variation in heart rate. EE = end-diastole at endexpiration; PI end-diastole at peak inspiration. = 670 CIRCULATION : ~ ~ ~ ~ . . : . . y: LABORATORY INVESTIGATION-VENTRICULAR mZ . . . S . ;: ..... .eEEe ..... .. 60 LEFT VENTRICUL.AR MINOR AXIS ANTEROR POSTERIOR DIAMETER ,rw) 4 /sec) ,v'VAVFYVX/ryMv\fvsvx( V ... ...:52Si:::E::: :y:::22iS:::X;:: ::;E;:fC::S; .: :; . . :;:E:f::: :::~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~. S.E. . . . .R ::~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~. AORTIC BLOOD fLOW .fESL . . .0 0.... H .. ... ... ...0A. . 49:. . A ... ..... ....SEiSE!;;iEdE; .s .. .... .... DIAMETER tI ....E j .E ; 0s... .... ESfRiES E; ....... i. ... EE)fE ... EiR . . .i ii 7R~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~. gi ::#~~~~~~~~~~~~~~~~~~~~~~~~~~~. .. .. LET VENTRIC ULAR MINOR AXIS . . ....... :: j pgE:9<:::;W: H iW::H r Q Q L i j u t r ^ i r i Q n r r- , ~ ~ ~ ~ ~ :~~ ~t: i j :.^-. A A 1 ...... .E.... LEFT VENTRICULAR MAJOR AXIS ... :WES :E)W;:S:;z:; ... E~~~~~~~~~~~~~~~~~~. .R . . ..EEi{ . . .....:EER:: E E:E S:ER : R .:... PERFORMANCE . . .E VVvVSrMVTAM E....:t:E VMWN\MA\Y4SNPYrVVtV SEPTAL-FREE WALL oDAMETER (mum Hg) RIGHT VENTRICULAR INTRACAVITARY PRESSURE ...... ............ ...E ..ai. Ei ... ..E':, ... rRANSVERSE LIAMETER iSa?; .. .... .t. ... .: 0 .....EiR ... .. ., 1\ . A ..j t.,' ::E:E: ......... RIGHT VENTRICULAR t. E i; ::. ........ .... .... .. .EE%:..Et )f~~~~~~~~~~~~~~iEE.:: ~~~~~ ~~~~~~~~~~..:: ... .... .... *R ..' ~~~~~~~~~~~~~~~~~~~. ,~ .. .A LI. '..l.... .;....:: ... :::: : ... . . ... ;iERi 0; iE :E,iRig~~~~~~~~~~~... :Et:i-i-:-,....... #E. R. . ,'ERE SR:.5:E R... '.....\E. . . .-SfER fiREtEa5diR -EfA,-EEiES-tEE giEEliEeE *.i'l; E.p....:Ei; iR 00 ;~ ~~~~~~~~~~~~~~~~~.. . . Rei. .i:E. ...EER ... E;Xkag20iE;:SiEE 2fiERS(ESS Ei EE .f .... Downloaded from http://circ.ahajournals.org/ by guest on April 29, 2017 iiiVg. ii2:i.i .. mmm Hg INTRAPLEURAL PRESSURE ...... ..... .... .. i E i2;e . . . . ....... ...R iEE-iE,E iER .. ..git; - :i : Z fi i, EEEE ....#' Eai Ei ;iEE i E R E * E i R * EgE':~~~~~~~~~~~~~~~~~~~~.. .......... ..... ... ~~.. . . :C: - iF 4, . . . .......: EEE~~~~~~~~~~~~~~~~~~~~~~...... . . ... ..| >g .._.. . . . .. 0-Er .. ..... mn g) : LEFT VENTRICULAR mm INTRACAVITARY PRESSURE EE 3. FIGURE Typical analog dimension, pressure, 70 70 ______________________ LV MINOR (mm) 60 87[ _ LV MAJOR DIAMETER (m{) RV MINOR 33 SEPTAL FREE WALL DIAMETER (mm) 23 RV -10 INTRACAVITARY PRESSURE (mm Hg) -10 -_ _ PI in figure 2. are as age of0.0 ± 0.5 mm Hg atend-expirationto1 1 1.7 ± 0.9 mm Hg at peak inspiration. During inspiration, left ventricular intracavitary end-diastolic and peak ejection pressures decreased by amounts similar to the changes in peak inspiratory intrapleural pressure (p K .01), while the corresponding right ventricular intracavitary pressures only decreased by approxione-half that amount (p < .01; table 1). The mately resulting left ventricular transmural end-diastolic pressure increased slightly (p < .05) and peak ejection pressure remained essentially constant (p > .3) _ _ -1 '-.. and flow data obtained from a conscious dog during two deep spontaneous respirations with heart rate controlled by atrial pacing. EE and ANTERIOR-POSTERIOR DIAMETER (mm) 60 LV MINOR 70 SEPTAL-FREE WALL DIAMETER f ,throughout _ LV 140 the respiratory cycle, while lar transmural pressures increased and INTRACAVITARY PRESSURE (mm HH) LV END-DIASTOLIC PRESSURE decreased during sures The (mmHg) inspiratory right ventricu- transseptal pres- < inspiration fall in end-diastolic transseptal sure resulted in leftward interventricular that reduced pres- septal shifting end-diastolic 0~~ INTRAPLEURAL PRESSURE displacement (mm Hg) time when during deep spontaneous inspirations, left a ventricular anterior-posterior -151 EE FIGURE 4. tamned from which heart Osec Representative digital a conscious rate with propranolol ;ic was controlled Vol. 72, No. 3, September dimension ob- n taousespi autonomic blockade pharmacolog dog and atropine. andpressuredata EE 198567 PI as are, in figure 2. major diameters increased ventricular constant was end-diastolic volume remained essentially slightly during the respiratory controlled increasing by slightly atrial (table cycle 2). when .06; pacing > Thus, heart rate figure 5), 671 A 1 OLSEN et al. TABLE 1 Mean end-diastolic and peak ejection hemodynamic data obtained during spontaneous deep respirations End-diastole EE PI PLP (mm Hg) RVP (mm Hg) LVP (mm Hg) RVTMP (mm Hg) LVTMP (mm Hg) TSP (mm Hg) 0.0+0.5 -11.7 -+0.9 5.9+1.1 -0.7 +1.6 10.0+1.1 -0.1 + 1.2 4.4+1.0 9.5 -+1.2 11.8+0.8 13.4-4-0.9 7.1±+ 1.0 3.7 + 1.0 B B A B 127.8+2.2 115.7 -+4.2 36.4+1.8 43.1 ±+2.0 130.0+4.8 129.9-+-4.6 88.2+5.0 82.3 ± 3.9 B B B B Peak ejection EE PI 36.9+3.1 -1.0+0.6 -12.6±+1.0 31.9 - 2.4 B B B Data are presented as mean + SEM for all 12 experiments. PLP = intrapleural pressure; RVP = right ventricular intracavitary pressure: LVP = left ventricular intracavitary pressure; RVTMP = right ventricular transmural pressure; LVTMP left ventricular transmural pressure; TSP = transseptal pressure; EE = end-expiration; PI = peak inspiration. Ap < .05; Bp < .01 by multivariate analysis. Downloaded from http://circ.ahajournals.org/ by guest on April 29, 2017 in two dogs, and decreasing slightly in the rest. The pattern of change in each individual dog varied from inspiration to inspiration about a narrow physiologically insignificant range. The end-ejection volume increased slightly on a more consistent basis from dog to dog with each inspiration. Stroke shortening (figures 3 and 4), peak aortic blood flow (figure 3), and stroke volume (p < .05; figure 5), however, still fell during inspiration. Diastolic left ventricular shape was significantly altered during inspiration, with most of the change resulting from leftward displacement of the interventricular septum. The altered left ventricular diastolic geometry during inspiration was indicated by the deTABLE 2 Mean end-diastolic and end-ejection dimension data obtained during spontaneous deep respirations a (cm) End-diastole EE PI %1 b (cm) d (cm) 7.63+0.20 6.32+0.21 2.35+0.11 7.65+0.20 6.33+0.20 2.27+0.11 --0.2+0.3 0.1 +0.4 -5.4±0.9 0.2 A End-ejection EE PI %1A RVD (cm) 3.00±0.29 3.25+0.30 9.0+ 1.3 B 7.50+0.19 5.91+t0.19 2.13+0.13 2.83+0.35 7.52+0.20 5.93+0.19 2.10±0.13 2.96+0.32 5.5 + 1.9 0.3 - 0.2 0.2 + 0.2 - 0.9 + 0.8 B Data are presented as mean ± SEM for all 12 experiments. a = basal-apical left ventricular major diameter; b = anterior-posterior left ventricular minor diameter; d = left ventricular septal displacement (segment OS from figure 1); RVD = right ventricular transverse diameter (observations from five experiments); %A = percent change determined as (PI- EE)/EE x 100%; other abbreviations and notes are as in table 1. 672 crease in left ventricular septal displacement (table 2). This resulted in an increased septal radius of curvature during inspiration, as shown in figure 6. Peak developed septal tension, however, decreased during inspiration (p < .05; table 3), while peak developed free wall tension remained unchanged (p > .3; table 3). Calculated peak aortic blood flow decreased by an average of 9% during inspiration (p < .01; table 3) and measured aortic blood flow showed similar changes (table 3). The inspiratory fall in measured peak ascending aortic blood flow (figure 7, A) and left ventricular stroke volume (figure 7, B) in the five aortic flow studies correlated with the fall in mean left ventricular intracavitary ejection pressure (p < .001) and did not correlate with peak left ventricular transmural pressure or with left ventricular end-diastolic volume during the respiratory cycle (p > . 1). Inspiratory correlations were observed between intrapleural pressure and left ventricular intracavitary pressure during diastole and systole (figure 7, C and D; p < .001). The pattern and direction of the changes in dimension, pressure, and flow observed during normal spontaneous respirations were qualitatively similar to those recorded during deep spontaneous respiration. The magnitude of peak inspiratory change during deep respiration was proportionally greater than that observed during normal spontaneous respiration (p < .01 by analysis of variance). Similarly, the results obtained during autonomic attenuation with propranolol and atropine were no different than those obtained during atrial pacing. Discussion The model of left ventricular geometry we used requires certain assumptions about cardiac shape in order CIRCULATION LABORATORY INVESTIGATION-VENTRICULAR PERFORMANCE 9CJ1Jr 11% 0 701 0 -o -o . _ 5030 {54.11 ±+4.14 155.84\ ±3.88/ E Downloaded from http://circ.ahajournals.org/ by guest on April 29, 2017 0 0 C 4) bh.. -o C) LLJ diameters measured in the current study, upon which assumptions about left ventricular shape were based, corresponded closely to the three principal axes (directions) of deformation derived from the eigenvector analysis of left ventricular geometry in an intact dog preparation by Walley et al.26 The deformations in these principal axes were similar in magnitude and direction to those observed in the present model.2' The interventricular septum was shifted leftward during diastole by the inspiratory augmentation in venous return to the right ventricle (table 2). This resulted in an altered left ventricular geometry that reduced chamber compliance, as demonstrated by the upward shift of the normalized pressure-volume curve in figure 8. This observation was consistent from dog to dog and from inspiration to inspiration in each dog. Detailed discussions of this methodology and the normalization procedures have been published previously.21 23-25 The reduction in left ventricular chamber compliance that occurs during direct ventricular interactions has been demonstrated previously,21 and indicates one effect of p a) _j J%J 250 h.. c,) 15(19.42 21.66 \+1.92/ EE \+2.23/ 1 I S PI FIGURE 5. Top, Left ventricular end-diastolic volumes recorded during the 12 experiments at end-expiration (EE) and peak inspiration (PI). The order of individual studies from top to bottom at EE is: 9, 1, 2, 11, 6, 5, 4, 3, 10, 8, 12, 7. Means ± SEM are shown in parentheses; p > .06. Middle, Left ventricular end-ejection volumes for all 12 experiments at EE and PI. The order of individual studies from top to bottom at EE is: 9, 1, 6, 7, 5, 11, 8, 4, 12, 3, 10, 7 (p > .35). Bottom, Left ventricular stroke volume recorded during the 12 experiments at EE and PI. The order of individual studies from top to bottom at EE is: 9, 2, 1, 11, 4, 3, 6, 5, 10, 12, 8, 7 (p < .05). that conclusions about volume changes can be derived. While it is difficult to validate these assumptions, the volume data we obtained by this technique correlate well with those obtained by two other independent methods, namely intraventricular balloon and electromagnetic determination of ascending aortic blood flow (see Appendix). The three principal left ventricular Vol. 72, No. 3, September 1985 1F F / A End-Expiration o---o Peak Inspiration FIGURE 6. Model of the left ventricle latitudinal plane representing change in the average end-diastolic shape during the respiratory cycle over all 12 experiments. During peak deep inspiration (open circles and broken line) the interventricular septum was shifted toward the left ventricle, indicating direct ventricular interaction. A, S, P, and F represent the anterior, septal, posterior, and lateral free walls, respectively. The end-diastolic latitudinal septal radius of curvature was greater during inspiration (RS2 = 4.41 cm 0.49 cm) than during end-expiration (RS, = 4.25 cm ± 0.49 cm; p < .05). 673 OLSEN et al. TABLE 3 Mean ejection data obtained during spontaneous deep respirations EE PI Ao max (ml sec -1) V1 max (ml sec -) T5 max (mm Hg cm) TF max (mm Hg cm) (mm Hg sec -1) 334.8 + 60.7 306.1 ± 55.6 8.4± 1.0 313.9± 15.8 285.2 ± 14.2 -9.0+ 1.1 349.0 ± 22.4 325.1 ± 21.2 -6.7± 1.5 401.4± 14.4 397.4 -+13.5 -0.8± 1.1 2429 ± 89 2249 ± 116 -6.5±2.0 B B A Pmax Data are presented as mean ± SEM for all 12 experiments. Ao max = peak measured ascending aortic blood flow (observations from five experiments); V, max ± peak calculated aortic blood flow; Ts max = peak left ventricular transseptal tension; TF max = peak left ventricular free wall tension; P max = peak positive left ventricular transmural dP/dt; other abbreviations and notes are as in tables 1 and 2. Downloaded from http://circ.ahajournals.org/ by guest on April 29, 2017 gravitational gradients throughout the chest, measurement of esophageal or peripheral pleural pressure may yield inaccurate results.27 The use of balloon or fluidfilled catheters may increase the magnitude of impact artifacts and baseline pressure shifts.20 28 In the present studies, the pericardium was left widely open to avoid the potential restrictive effects of scarring or reapproximation of surgically manipulated pericardium. At postmortem examination, the pericardium remained widely open and nonadherent to the right or left ventricles. The effect of an intact pericardium on the results of the present study probably would have been minimal since there were no large changes in ventricular volumes. Moreover, changes in intrapericardial pressure during respiration closely parallel intrapleural pressure changes in the conscious dog.27 29 Opening the pericardium in an intact, closed- respiration on cardiac function. Figure 8 also attests to the need for accurate measurement of pleural pressure in the assessment of ventricular function, as well as the need for differentiation of end-expiratory from peak inspiratory cardiac cycles in the analysis of diastolic properties. The accurate measurement of pleural pressure was critical in this study. Pleural pressure should be measured on the surface of the heart at approximately the same vertical level as the intracavitary manometer. The placement of the pleural micromanometer within a large-bore silicone rubber tube with multiple side holes protected the manometer face from motion artifacts but still allowed free communication with the potential space of the pleural cavity. In this manner, reproducible and accurate measurements were made of the pleural pressure affecting cardiac function. Because of the 20, 'ARn. A 360 I cyb E O E 340 1 . 0 W W U O 320 * CD y -* 3.826x - 153 122 0.647 p/ -<.op00I r .R300 - . 280' 35 1 B. 34 / .2E vc _ w 32 * um y 0.241x+1.182 n 48 r-.r0.721 p .. <.001 V. 115 120 125 130 135 Meon Left Ventricular Ejection Pressure (mmHg) 674 140 -20 -15 -1O -5 Pleurol Pressure (mmHg) FIGURE 7. A, Representative relationship between mean left ventricular intracavitary ejection pressure and peak ascending aortic blood flow during deep spontaneous respirations in one experiment. Linear regression coefficients for the five experiments in which ascending aortic blood flow was measured were m = 8.045 + 3.860 and b = -772.220 ± 485.785 (r . .503, p < .005). B, Relationship between mean left ventricular intracavitary ejection pressure and left ventricular stroke volume measured from ascending aortic blood flow during the same deep spontaneous respirations as in A. For all five experimentsm = 0.302 ± 0.089andb = -18.249 ± 10.950 (r ' .560, p < .01). C, Representative end-diastolic relationship between left ventricular intracavitary pressure and simultaneous intrapleural pressure during the same deep spontaneous respirations as in A. For all five experiments m = 0.922 + 0.084 and b = 12.593 ± 2.438 (r . .835, p < .001). D, Same relationship as in A except during ejection. For all five experiments m = 1.370 + 0.230 and b = 142.067 ± 5.733 (r . .835, p < .001). CIRCULATION LABORATORY INVESTIGATION-VENTRICULAR PERFORMANCE Downloaded from http://circ.ahajournals.org/ by guest on April 29, 2017 0.10 0.15 LV Volume Strain (CE ) FIGURE 8. The effects of respiration on the normalized left ventricular diastolic pressure-volume relationship in one experiment. The solid curve was obtained by fitting all end-diastolic end-expiration data during a transient vena caval occlusion to the exponential function P = (eP' - 1), where a and are nonlinear coefficients describing the curve and were 0.837 and 13.188, respectively. Superimposed on this curve are data digitized at 200 Hz from two separate cardiac cycles: one from end-expiration (EE, closed circles) and one from peak inspiration (PI, open circles). Peak inspiratory intrapleural pressure was - 12.7 mm Hg. a chest canine preparation had no effect on right and left ventricular pressures, left ventricular volumes, or ejection fraction, suggesting that at normal end-diastolic volumes and pressures, the pericardium has minimal influence on ventricular function.26 An intact pericardium may augment inspiratory leftward septal shifting via the direct ventricular interaction that results from increased right ventricular end-diastolic volumes. However, it is doubtful that such direct ventricular interaction significantly impairs left ventricular function or contributes to the inspiratory fall in left ventricular stroke volume. 19 In a series of unpublished studies from this laboratory in which the pericardium remained intact, the inspiratory changes in the principal measured diameter were similar in direction and magnitude to those observed in the present study.29 The marked respiratory variation in heart rate observed during deep, and to a lesser extend during normal respiration, resulted in rather large fluctuations in beat-to-beat left ventricular end-diastolic volume. Several mechanisms have been proposed for this.3032 Both atrial pacing and pharmacologic autonomic attenuation with propranolol and atropine effectively ablated the respiratory change in heart rate and neither resulted in a significant change in left ventricular end-diastolic Vol. 72, No. 3, September 1985 volumes (in some dogs volume increased slightly while in others it decreased minimally). Similar results have recently been observed on radionuclide ventriculograms from healthy human subjects during deep inspirations against resistance.33 The inspiratory decrease in left ventricular end-diastolic volume has been thought to result from increased pooling of blood in the lungs'7 or delayed pulmonary transit time of blood.7 34 Both would cause a decrease in left ventricular end-diastolic volume (preload) and account for the subsequent fall in left ventricular stroke shortening and peak aortic blood flow that is so apparent in figure 3. Increases in heart rate alone can cause a fall in left ventricular end-diastolic and stroke volumes.22 30 However, when heart rate was kept constant by atrial pacing or by pharmacologic autonomic attenuation, as demonstrated in figures 3 and 4, the left ventricular end-diastolic volume remained relatively unchanged, suggesting that under these conditions, increased venous pooling in the lungs or delayed pulmonary transit time was insufficient to prevent adequate left ventricular filling and played only a minor physiologic role. In addition, leftward shifting of the interventricular septum did not seem to significantly inhibit left ventricular filling when heart rate was kept constant. This is graphically apparent in figure 3. During the prolonged second inspiration, the interventricular septum initially was shifted leftward (reduced minor-axis septal-free wall diameter), with augmented venous return to the right ventricle (increased right ventricular transverse diameter). As inspiration progressed, augmented venous return became less apparent and the septum shifted back to the right, presumably as left ventricular end-diastolic volume increased due to delayed return of the increased pulmonary pooling of blood. Aortic blood flow, however, continued to decrease apparently independent of these events. Similar changes in left ventricular end-diastolic volume and aortic blood flow were observed in several dogs during prolonged deep inspirations. Another proposed hypothesis has been that leftward shifting of the interventricular septum during inspiration alters ventricular geometry and increases the geometric component of left ventricular afterload.'8 '9 Flattening of the interventricular septum might increase the septal radius of curvature, augment septal wall tension, and impede left ventricular stroke volume during ejection. Although the present studies demonstrated an inspiratory leftward shifting of the septum with altered diastolic geometry that persisted into systole, the increase in septal radius of curvature 675 OLSEN et al. Downloaded from http://circ.ahajournals.org/ by guest on April 29, 2017 was small and was outweighed by the larger fall in the transseptal pressure gradient (table 1). Thus, left ventricular septal wall tension actually decreased during inspiration (table 3), and the augmentation in the geometric component of left ventricular afterload from septal shifting did not occur. Yet another proposed hypothesis is that the inspiratory decline in pleural pressure increased left ventricular transmural pressure (left ventricular intracavitary pressure minus pleural pressure), causing a fall in stroke volume.6 9, 12 20. 3436 Intracavitary left ventricular ejection pressure decreased by an amount similar to that by which pleural pressure is decreased during inspiration such that left ventricular transmural ejection pressure remained unchanged (table 1). Thus, augmentation of the intraventricular pressure component of left ventricular afterload did not appear to account for the inspiratory fall in left ventricular stroke volume. Similar observations have been made by others.7" From the present data, an alternative explanation is proposed for the inspiratory fall in left ventricular stroke volume. The correlations between peak aortic blood flow, left ventricular stroke volume, and mean intracavitary left ventricular ejection pressure (figure 7, A and B) has led us to the hypothesis that the intracavitary left ventricular pressure referenced to atmospheric pressure is actually the effective ejection pressure of the left ventricle and that the inspiratory decrease in this pressure accounts for the fall in stroke volume. During diastole, the heart is the chamber at the end of the blood flow and pleural pressure is the appropriate external pressure. However, during ejection, when the aortic valve is open and the left ventricle is in continuity with the systemic arterial system, the peripheral vasculature is at the end of the blood flow and atmospheric pressure is the appropriate external pressure. During inspiration, the hydraulic force effecting ejection (intracavitary left ventricular pressure) is decreased by an amount equal to the decline in intrapleural pressure, and left ventricular stroke volume falls as a result of the decrease in this effective left ventricular ejection pressure. Intrathoracic aortic pressure referenced to atmospheric pressure is reported to fall during inspira20 but to a lesser degree than the inspiratory tion,6, 12h reduction in intracavitary left ventricular pressure. This is reported to increase left ventricular afterload and decrease stroke volume. In unpublished observations from this laboratory simultaneously measured high-fidelity left ventricular, ascending and descending thoracic aortic, and abdominal aortic pressures were all observed to fall by a similar amount equal to 676 the inspiratory decline in pleural pressure during normal and deep inspiration. Thus, the transmural pressures referenced to pleural pressure at these four simultaneous points of measurement along the central and systemic vascular system did not rise during inspiration, but instead remained essentially unchanged. An increase in left ventricular or transthoracic aortic afterload that might account for the inspiratory fall in stroke volume was not apparent in these studies, or in others.7" The impedance in effective left ventricular ejection pressure induced by the inspiratory decline in pleural pressure had an effect on left ventricular stroke volume similar to that of an increase in left ventricular afterload, but it apparently occurred by a different mechanism since no measurable increase in transmural left ventricular or transthoracic aortic afterload could be demonstrated. It is therefore more appropriate to refer to the inspiratory effect of pleural pressure on left ventricular function as an impedance of the effective ejection pressure rather than an increase in left ventricular afterload in terms of systolic wall stress.33 Right ventricular ejection is not effected during inspiration by the same mechanism that effects left ventricular ejection. During right ventricular ejection, when the pulmonary valve is open, the right ventricle is in continuity with the pulmonary circulation and the left atrium, all of which are subjected to the same inspiratory fall in intrapleural pressure. Thus, pleural pressure is the appropriate external pressure for the right ventricle during ejection and during diastole. Accordingly, during inspiration, the hydraulic force effecting ejection from the right ventricle is not decreased relative to its appropriate external pressure and right ventricular stroke volume would not be expected to fall on the basis of a decreased effective ejection pressure. In fact, the effective ejection pressure of the right ventricle (right ventricular transmural pressure) was increased during inspiration (table 1) as a result of increased venous return (preload), and right ventricular stroke volume was augmented. Right ventricular cavitary volume was not assessed directly in the current study, although increases in the end-diastolic transverse diameter during inspiration (table 2) were believed to represent increased right ventricular enddiastolic volume and were found to correlate linearly with postmortem right ventricular intracavitary balloon volumes (see Appendix). Similar results have been reported by others.19 Clinically, an exaggeration of the normal inspiratory decline in left ventricular stroke volume may result in pulsus paradoxus, the absence of a peripheral pulse despite the presence of a cardiac contraction.38 CIRCULATION LABORATORY INVESTIGATION-vENTRICULAR PERFORMANCE Downloaded from http://circ.ahajournals.org/ by guest on April 29, 2017 Conditions that accentuate the swings in pleural pressure (such as asthma, pulmonary embolism, or pulmonary edema), and conditions that increase the interactive coupling between the right and left ventricles (such as cardiac tamponade or acute right heart failure) may result in either pulsus paradoxus or an increased widening of the inspiratory fall in peak systemic blood pressure. Conversely, the marked increases in the pleural pressure that occur with coughing may produce reversed pulsus paradoxus, the presence of a peripheral pulse in the absence of a cardiac contraction.39'40 Conditions that elevate the intrathoracic pressure, such as positive pressure ventilation, Valsalva maneuver, or coughing, augment left ventricular stroke volume as well as forward flow of blood from the thoracic aorta via a thoracic pump mechanism.40 Factors elevating pleural pressure augment left ventricular pressure and favor left ventricular ejection, while conditions reducing pleural pressure lower the effective left ventricular ejection pressure and impede left ventricular stroke volume. In this regard, deep inspiration may be referred to as a reverse thoracic pump mechanism. Thus, a hypothesis is proposed that is consistent with, as well as an extension of, the thoracic pump mechanism to explain the long-observed differential effects of inspiration on right and left ventricular stroke volumes. Conceptually, this hypothesis provides a more accurate explanation of cardiorespiratory interaction during inspiration than has previously been offered. Other mechanisms, such as altered preload or afterload, appear to contribute only secondarily, if at all, to the inspiratory fall in left ventricular stroke volume. The principal factor diminishing left ventricular stroke volume during inspiration is the inspiratory fall in the effective intracavitary ejection pressure of the left ventricle. Appendix The modified ellipsoid used in the current studies to model left ventricular shape and volume represents the concatenation of two ellipsoidal segments and has been discussed in detail previously.21 The current model accurately predicted left ventricular stroke volume over a wide range of left ventricular volumes and under various conditions of ventricular interaction with both high and low right ventricular volumes. The stroke volumes and flows calculated from the dimension measurements as - dV1/dt correlated very well over a wide range of physiologic volumes, with minimal variability when compared with the stroke volumes and flows measured by an ascending aortic electromagnetic flow probe.2' The dimension transducers were positioned at approximately 90 degree points around the latitudinal and longitudinal circumferences of the left ventricle. The true three-dimensional position of each transducer was determined in separate validation studies by measurement with the linear chords from all possible paired combinations of the septal and epicardial crystals. The results of one such experiment are shown in figure 9, where the Vol. 72, No. 3, September 1985 true three-dimensional position of each transducer determined by the chord measurements was compared with the assumed position of these transducers based on the double hemiellipsoidal model (figure 1). The difference in volume calculated from the assumed model and that computed from the actual position based on a three-point derivation of an ellipsoidal segment was minimal (0.9 to 1.8 ml) and accounted for less than a 3% difference in corresponding calculated chamber volumes. In four studies, in which the hearts were excised with the ultrasonic dimension transducers still in place and before determination of left ventricular wall volume displacement, both atria, the tricuspid and mitral valves, and chordae tendineae were removed. The semilunar valve orifices were individually sutured closed, compliant balloons attached to Lucite disks were introduced into each ventricle, and the sewing rings of the disks were sutured to the anuli of the tricuspid and mitral valves. The excised heart was then suspended in a water bath and left ventricular balloon volumes were varied over a wide range at various right ventricular balloon volumes while recording left and right ventricular ultrasonic dimensions. At various levels of right ventricular balloon volume ranging from 0 to 60 ml, the correlation between the absolute measured and calculated left ventricular chamber volumes was excellent, and the line of regression was very near the line of identity, despite marked differences in relative septal position (figure 10, A). In a similar fashion, right ventricular transverse diameter was linearly related to right ventricular cavitary balloon volume (figure 10, B). These data, coupled with those published previously,2' indicate the validity of the current model in accurately assessing left ventricular volume and geometry. We are grateful to Mr. James Bradsher and his staff for technical assistance, to Ms. Sandra Justice for preparing the manuscript, and to the Duke Audiovisual Department for the illustration. POSTERIOR BASE BASE POSTERIOR -------- APEX B SEPTAL TERIOR ~ ~ ~ - FREEWALL APEX FIGURE 9. Comparison of left ventricular geometry derived from the position of the dimension transducers assumed by the model (thin solid lines) with geometry obtained from the actual position of the dimension transducers calculated from the chord measurements (broken and heavy solid lines). A, Latitudinal plane; B, longitudinal plane through the anterior and posterior transducers; C, longitudinal plane through the septal and free wall transducers. The difference in the actual and assumed volumes calculated by the two methods was less than 3%. 677 OLSEN et al. r - U. Jvo} _ 60 f r - RV Chamber Volume : mI '4.0 - V= 60 m1 20 40 3.- 40 - .- > 40 6* 20 Meosured LV Chamber Volume (m1) 20 0 80 40 60 80 sured RV Chomber V@olume (mli) Downloaded from http://circ.ahajournals.org/ by guest on April 29, 2017 FIGURE 10. A, Calculated chamber volume vs measured left ventricular intracavitary balloon volume from four postmortem studies at various levels of right ventricular volume. 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In Fenn WD, Rahn H, editors: Handbook of physiology, vol II, section 3. 1965, Washington, D.C., American Physiological Society, ch 52, pp 1875-1886 40. Niemann JT, Rosborough J, Hansknecht M, Brown D, Criley JM: Cough-CPR: Documention of systemic perfusion in man and in an experimental model: a "window" to the mechanism of blood flow in external CPR. Crit Care Med 8: 141, 1980 Downloaded from http://circ.ahajournals.org/ by guest on April 29, 2017 Vol. 72, No. 3, September 1985 679 Diminished stroke volume during inspiration: a reverse thoracic pump. C O Olsen, G S Tyson, G W Maier, J W Davis and J S Rankin Downloaded from http://circ.ahajournals.org/ by guest on April 29, 2017 Circulation. 1985;72:668-679 doi: 10.1161/01.CIR.72.3.668 Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 1985 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7322. 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