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
Electrocardiography wikipedia , lookup
Cardiac contractility modulation wikipedia , lookup
Lutembacher's syndrome wikipedia , lookup
Myocardial infarction wikipedia , lookup
Heart failure wikipedia , lookup
Mitral insufficiency wikipedia , lookup
Hypertrophic cardiomyopathy wikipedia , lookup
Atrial septal defect wikipedia , lookup
Quantium Medical Cardiac Output wikipedia , lookup
Ventricular fibrillation wikipedia , lookup
Arrhythmogenic right ventricular dysplasia wikipedia , lookup
135 Effect of Acutely Increased Right Ventricular Afterload on Work Output From the Left Ventricle in Conscious Dogs Systolic Ventricular Interaction Michael P. Feneley, Craig O. Olsen, Donald D. Glower, and J. Scott Rankin Downloaded from http://circres.ahajournals.org/ by guest on June 18, 2017 In seven conscious, chronically instrumented dogs, left ventricular volume was calculated with an ellipsoidal model from the anteroposterior, septal-free wall, and base-to-apex left ventricular dimensions, measured by implanted ultrasonic transducers. Matched micromanometers measured left and right ventricular transmural and transseptal pressures. Ventricular pressures and volumes were varied by inflation of implanted vena caval and pulmonary arterial occluders. When compared with vena caval occlusion at matched left ventricular end-diastollc volumes, graded pulmonary arterial occlusions were associated with higher right ventricular systolic pressures, reduced left-to-right transseptal systolic pressure gradients, and leftward systolic septal displacement, with increased septal-free wall segment shortening (all p<0.05). Graded pulmonary arterial occlusions, like vena caval occlusions, reduced left ventricular end-diastolic volume, but left ventricular stroke work at a given end-diastolic volume was greater during pulmonary arterial occlusions (2,674±380 10 erg) than during vena caval occlusion (l,886±450 10 erg, /><0.05). These data indicate that, while transient pulmonary arterial occlusion reduces left ventricular preload, the concomitant increase in right ventricular systolic pressure, which is the pressure external to the interventricular septal segment of the left ventricle, augments septal shortening and assists left ventricular pump function at a given preload through direct systolic ventricular interaction. {Circulation Research 1989;65:135-145) I nteractions between the left and right ventricles have long been recognized to occur during diastole.1 Diastolic ventricular interaction may be viewed as a volume distribution phenomenon between two chambers that are separated by a mobile wall, the interventricular septum. Increased filling of either ventricle alters the transseptal pressure gradient and displaces the interventricular septum toward the opposite ventricle, thereby decreasing the latter's diastolic From the Departments of Surgery and Physiology, Duke University Medical Center, Durham, North Carolina. Supported in part by National Institutes of Health, National Heart, Lung, and Blood Institute grants HL-09315 and HL29436 and SCOR Grant HL-17670. M.P.F. is the recipient of a Fulbright Postdoctoral Scholarship, a Neil Hamilton Fairley Fellowship from the National Health and Medical Research Council of Australia, and a Telectronics Overseas Fellowship from the Royal Australasian College of Physicians. Address for correspondence: J. Scott Rankin, MD, Associate Professor, Department of Surgery, Box 3851, Duke University Medical Center, Durham, NC 27710. Received June 11, 1987; accepted December 10, 1988. compliance.2-12 This effect is enhanced by the intact pericardium.6.8,13,14 Because increased filling of either ventricle impedes filling of the other, diastolic ventricular interaction has been aptly described as "ventricular interference." 6 There is far less consensus concerning the nature and significance of systolic ventricular interactions.15 Considerable evidence supports the view that left ventricular contraction contributes to right ventricular systolic function,16-25 although some dissent from this view.26 Under normal loading conditions, right ventricular contraction has been thought to exert little direct effect on left ventricular systolic function.24'26 Several studies have addressed the issue of whether abnormal right ventricular loading conditions influence left ventricular systolic function, but the conclusions have been somewhat conflicting.2'7'13'27-31 In part, the different conclusions reached in these studies reflected differences in the methods used to assess left ventricular systolic function. For example, left ventricular pump function curves were observed 136 Circulation Research Vol 65, No 1, July 1989 to be depressed by right ventricular volume overload when left ventricular end-diastolic pressure was employed as the index of preload.2 Subsequent studies suggested, however, that the apparent depression of left ventricular systolic function under abnormal right ventricular loading conditions reflected the concomitant decrease in the diastolic compliance and end-diastolic volume of the left ventricle due to diastolic ventricular interaction: indexes of left ventricular systolic function were not depressed when the reduced end-diastolic volume (preload) was accounted f o r . - Downloaded from http://circres.ahajournals.org/ by guest on June 18, 2017 Left ventricular stroke work, the energy output from the left ventricular chamber during contraction, has recently been shown to be a linear function of the end-diastolic volume in conscious dogs.32 If the effects of altered right ventricular loading conditions on left ventricular systolic function could be accounted for entirely by the concomitant reduction in left ventricular end-diastolic volume, then the linear stroke work-end-diastolic volume relation of the left ventricle would not be perturbed by altered right ventricular loading conditions. Left ventricular systolic pressure has been observed to increase, however, after sudden constriction of the pulmonary artery.28 Moreover, right ventricular systolic hypertension has been observed to cause systolic displacement of the interventricular septum into the left ventricular cavity,31-33-35 which might be expected to increase the stroke volume displaced from the left ventricular chamber at a given end-diastolic volume. Since stroke work is the product of stroke volume and developed pressure, the hypothesis tested in this study was that an acute increase in right ventricular afterload would increase the stroke work output from the left ventricular chamber at a given (albeit reduced) left ventricular end-diastolic volume by direct systolic ventricular interaction. Materials and Methods Experimental Preparation Seven healthy adult dogs (19-30 kg) were anesthetized (thiamylal sodium, 25 mg/kg i.v.), intubated, and ventilated with a volume respirator (Bennett MA-1, Puritan-Bennett, Los Angeles, California). Under sterile conditions, a left thoracotomy was performed through the fifth intercostal space. Pulsetransit ultrasonic dimension transducers were positioned across the anteroposterior and septal-free wall minor axis diameters, and the base-to-apex major axis diameter of the left ventricle, as described previously.31 In three dogs, an additional transducer was positioned on the right ventricular free wall to permit measttrement of the right ventricular septalfree wall diameter. The septal transducer (1.5 mm o.d. cylinder) was placed through the tract of a 19-gauge needle that was introduced into the septum just to the right of the left anterior descending coronary artery, and the transducer was positioned near the right ventricular endocardia! surface mid- way between the anterior and posterior transducers. The remaining transducers (5 mm o.d. hemispheres) were sutured to the epicardium under direct vision. Silicone rubber pneumatic occluders were positioned about both venae cavae and about the main pulmonary artery. Heparin-filled silicone catheters (2.6 mm i.d.) were implanted in the base of the left atrium and the apex of the right ventricle. A similar catheter with multiple side holes was placed in the pleural space adjacent to the left ventricular epicardial surface. The pericardium was left widely open, and the transducer leads, catheters, and occluder tubing were exteriorized dorsal to the thoracotomy, which was repaired in multiple layers. Procaine penicillin G (600,000 IU i.m.) and dihydrostreptomycin (250 mg i.m.) were administered daily. Data Acquisition and Experimental Protocol After a recovery period of 7-14 days, each dog was sedated lightly (morphine sulfate, 5 mg i.m.) 1 hour before data acquisition and was studied in the conscious state as it lay quietly on its right side. Detailed descriptions of the operating characteristics of the equipment used for data acquisition have been given in several previous reports.31'32'3* The dimension transducers were coupled to a sonomicrometer designed and built in our laboratory. Three micromanometers (PC-350 or MPC-500, Millar Instruments, Houston, Texas), which had been prewarmed (38° C), balanced, and calibrated simultaneously against a water column, were passed via the implanted silicone catheters to obtain the left ventricular, right ventricular, and pleural pressures. Resultant manometer drift was less than 0.5 mm Hg in all studies. Analog data were digitized at 200 Hz, either in real time (model 1012 A/D converter, ADAC) or from FM tape. Data were recorded under control conditions, during transient maximal vena caval occlusion, and during graded pulmonary arterial occlusions. Sufficient time was permitted for return to stable control conditions between interventions. In three dogs, the protocol was repeated after attenuation of the autonomic nervous system with propranolol (1-2 mg/kg i.v.) and atropine (0.4 mg/kg i.v.). At the conclusion of each study, the dog was killed by intravenous injection of potassium chloride under deep barbiturate anesthesia. The heart was excised, and proper position of the transducers was verified. The volume of the left ventricle was measured by water displacement after excising the atria, right ventricular free wall, aortic and mitral valves, and chordae tendineae. Data Analysis Analysis of digitized data was performed on a microprocessor (model PDP 11/23, DEC) with interactive programs developed in our laboratory. Left and right ventricular free wall transmural pressures were calculated as the differences between the Feneley et al Systolic Ventricular Interaction Downloaded from http://circres.ahajournals.org/ by guest on June 18, 2017 respective chamber pressures and pleural pressure. The left-to-right pressure gradient across the interventricular septum, the transseptal pressure, was determined by subtracting right ventricular pressure from left ventricular pressure. As described in detail previously,32 the phases of each cardiac cycle were defined with reference to the first time derivative of left ventricular transmural pressure (dP/dt), which was computed from the digital pressure waveform as a running five-point polyorthogonal transformation. Left ventricular volume (V) was calculated by fitting the epicardial major (a), anteroposterior minor (b), and septal-free wall minor (c) axis dimensions of the left ventricle to a modified ellipsoidal shell model31-37 and subtracting ventricular wall volume (Vwau). The formula for the volume of the modified ellipsoid is mathematically equivalent to that for a general ellipsoid.31 Thus: V=7T/6 abc-Vw.ii (1) The equatorial plane of the left ventricular minor axis was represented by a two-compartment model described previously.31 The left ventricular free wall was assumed to deform uniformly according to the left ventricular transmural pressure, while the interventricular septum was assumed to deform according to the transseptal pressure. Consequently, the radius of curvature of the free wall in this plane (Rpw) was assumed to be uniform and equal to one half of the anteroposterior minor axis dimension (b): Rpw=b/2 (2) In this two-compartment model, therefore, the contribution of alterations in septal position to the total septal-free wall dimension (c) was calculated by subtracting the instantaneous R ^ : d=c-b/2 (3) where d is the distance from the septum to the center of curvature of the left ventricular free wall. Both the theoretical basis for the derivation of Equations 1-3 and empirical validation of the geometric model on which these derivations were based have been reported in detail previously.31*37 Left ventricular stroke work (SW) was calculated as the integral of left ventricular transmural pressure (P) with respect to cavitary volume over each cardiac cycle: SW=/P • dV (4) The relation between left ventricular stroke work and end-diastolic volume (EDV) during vena caval occlusion was determined by linear regression analysis, as described previously,32 so that data were fitted to the formula: SW=MW (EDV-V W ) (5) 137 where M w and V w are the slope and x-intercept, respectively, of the stroke work-end-diastolic volume relation. Stroke work was also plotted against end-diastolic volume during graded pulmonary arterial occlusions. Once the right ventricular pressure had stabilized at a new level during pulmonary arterial occlusion, however, the variation in leftventricular end-diastolic volume was usually small. Each stroke work data point obtained during a stable pulmonary arterial occlusion was compared, therefore, with the stroke work predicted at the same end-diastolic volume by the linear stroke work-end-diastolic volume relation obtained during vena caval occlusion. The validity of this comparison depends on the reproducibility of repeated determinations of the stroke work-end-diastolic volume relation under constant loading conditions (see "Appendix"). Comparisons of cardiac dimension, volume, and pressure data were made between the two occlusion states from cardiac cycles with similar end-diastolic volumes. Statistical comparisons were made by Bonferroni-adjusted paired t tests. Results are expressed as mean±SEM. Results Representative, dynamic cardiac dimension and pressure waveforms from cardiac cycles with similar left ventricular end-diastolic volumes during vena caval and pulmonary arterial occlusions are shown in Figure 1. Left ventricular pressurevolume loops obtained in the same study during the two occlusion states are shown in Figures 2A and 2B. In panel C, one of the loops obtained during the steady-state phase of pulmonary arterial occlusion from panel B has been superimposed on the same loops shown in panel A during vena caval occlusion. In panel D, left ventricular stroke work (the area of the pressure-volume loops in panels A and B) is plotted against end-diastolic volume for the two occlusion states. As documented previously,32 the stroke work-end-diastolic volume relation during vena caval occlusion was highly linear; the mean linear correlation coefficient for this series of experiments was 0.98±0.01. The control beats preceding the onset of pulmonary arterial occlusion in panel D of Figure 2 lie on the regression line obtained during vena caval occlusion. With the onset of pulmonary arterial occlusion, however, the stroke work-end-diastolic volume relation shifts rapidly leftward over several beats, so that at any given end-diastolic volume, left ventricular stroke work is greater during pulmonary arterial occlusion than during vena caval occlusion. Similarly, as illustrated in panel C, at a given end-systolic left ventricular volume, the end-systolic transmural pressure is greater during pulmonary arterial occlusion than during vena caval occlusion. Figure 3 demonstrates that the increased left ventricular stroke work generated from a given end-diastolic volume during the pulmonary arterial occlusion shown in Figure 2 resulted from an increase in both the mean 138 Circulation Research Vol 65, No 1, July 1989 VCO PAO 15 LV BASE-APEX DIMENSION(cm) w LV ANTE RO- POSTERIOR DIMENSION (cm) LV SEPTAL-FREE WALL DIMENSION (cm) Downloaded from http://circres.ahajournals.org/ by guest on June 18, 2017 LV SEPTAL DISPLACEMENT (cm) U 36 RV SEPTAL-FREE WALL DIMENSION (cm) 2J ISO TRANSMURAL PRESSURE (mmHj) LV RV LV TRANSSEPTAL PRESSURE (rimHg) FIGURE 1. Representative left ventricular (LV) and right ventricular (RV) dynamic dimension and pressure waveforms recorded during vena caval occlusion (VCO) and pulmonary arterial occlusion (PAO) for cardiac cycles with similar left ventricular end-diastolic volumes. developed left ventricular ejection pressure and the stroke volume when compared with vena caval occlusion. The pulmonary arterial occlusion illustrated in Figure 2 was of relatively mild grade, as evidenced by the small resultant decrement in the transseptai pressure when compared with the vena caval occlusion state (Figure 1). With more severe grades of pulmonary arterial occlusion, however, the stroke work-end-diastolic volume relation continued to shift leftward during the period when left ventricular end-diastolic volume was decreasing, thus precluding valid linear regression analysis of the data obtained during most pulmonary arterial occlusions. In Figure 4, representative examples of the stroke work-end-diastolic volume data obtained during the steady-state phase of several grades of pulmonary arterial occlusion are compared with the corresponding regression lines obtained during vena caval occlusions. In a given animal, increasing grades of pulmonary arterial occlusion produced progressively greater leftward shifts of the left ventricular stroke work-end-diastolic volume relation. As illustrated in Figure 1, even mild grades of pulmonary arterial occlusion resulted in characteristic alterations in the right and left ventricular pressures and in left ventricular geometry when compared with vena caval occlusion. During pulmonary arterial occlusion, the diastolic and systolic transmural pressures of the right ventricle and, to a lesser extent, of the left ventricle increased, with a consequent reduction in the corresponding transseptai pressures. Consistent with these alterations in distending pressures, the right ventricular septalfree wall dimension increased and the left ventricular septal-free wall dimension decreased during pulmonary arterial occlusion due to leftward septal displacement, while the anteroposterior minor and base-to-apex dimensions of the left ventricle increased. The relations between the septal-free wall and the anteroposterior minor axis dimensions of the left ventricle at end diastole and at end ejection during the two occlusion states in one study are shown in Figure 5. As observed previously,31 these relations were shifted to the right during pulmonary arterial occlusion, indicating that for any given anteroposterior dimension, the septal-free wall dimension was shorter during pulmonary arterial occlusion than during vena caval occlusion, whether measured at end diastole or at end ejection. Moreover, because of the free wall component of the septal-free wall dimension (b/2 in Equation 3) at any given volume tended to increase during pulmonary arterial occlusion, the shortening of the septal-free wall dimension was attributable entirely to shortening of its septal component (d in Equation 3). The mean hemodynamic and dimensional data from all paired vena caval occlusion and steadystate pulmonary arterial occlusion studies are presented in Table 1. Although the possibility of reflex changes in autonomic tone during pulmonary arterial occlusion cannot be eliminated, there was no significant difference between the heart rates observed during the two occlusion states. Moreover, pharmacological attenuation of the autonomic nervous system did not alter the relative impact of pulmonary arterial and vena caval occlusions on left ventricular hemodynamics and dimensions, as observed previously.31 When compared with vena caval occlusion at the same left ventricular enddiastolic volume, pulmonary arterial occlusion augmented left ventricular stroke work by an average Feneley et al Systolic Ventricular Interaction 139 PAO vco 2. Panel A: Left ventricular (LV) pressure-volume loops recorded during a vena caval occlusion (VCO). Panel B: Left ventricular pressurevolume loops recorded during a partial pulmonary arterial occlusion (PAO) to a new steady-state right ventricular pressure. Panel C: One of the pressurevolume loops from the steady-state phase of pulmonary arterial occlusion in panel B has been superimposed on the loops obtained during vena caval occlusion in panel A. Panel D: The relations between left ventricular stroke work and end-diastolic volume for the two occlusion states. The relation shifts to the left with the onset of pulmonary arterial occlusion. FIGURE Downloaded from http://circres.ahajournals.org/ by guest on June 18, 2017 LV VOLUME (ml) LV END-WAST0L1C VOLUME (ml) 42%, peak left ventricular transmural pressure by an average 16%, and stroke volume by an average 30%. Ejection phase shortening of the left ventricular septal-free wall dimension increased during pulmonary arterial occlusion, due entirely to increased shortening of its septal component (d in Equation 3). On the other hand, shortening of the anteroposterior minor and base-to-apex left ventricular dimensions was not altered significantly, again suggesting that the improved left ventricular performance was not dependent on increased autonomic tone. The enhanced septal shortening with pulmonary arterial occlusion was consistent with the significant reductions in both the peak systolic transseptal pressure and the peak systolic transseptal/transmural pressure ratio of the left ventricle (Figure 6). Discussion Evidence from two previous studies suggested that when the effects of altered right ventricular loading conditions on left ventricular preload are accounted for, right ventricular pressure overload, or combined pressure and volume overload, does not impair left ventricular systolic function.27-31 Although transient pulmonary arterial occlusion decreases left ventricular preload, and thus stroke work, the highly linear and reproducible relation between stroke work and end-diastolic volume32 (see "Appendix") permitted a comparison to be made in the present study between left ventricular stroke work with high right ventricular systolic pressures and stroke work with low right ventricular systolic pressures at the same end-diastolic volume. The new finding from this study is that an acute increase in right ventricular pressure significantly increases the work output from the left ventricular chamber at a given end-diastolic volume. The left ventricular model employed to determine left ventricular volume in this study has been described and validated in previous reports from this laboratory,31-37 and very similar models have been validated by others.30-38 Because of the relatively small changes in left ventricular end-diastolic volume during the steady-state phase of pulmonaiy arterial occlusion in most cases, it was not possible to apply linear regression analysis to the steadystate data to determine quantitatively whether the increment in left ventricular stroke work with pulmonary arterial occlusion resulted solely from a parallel leftward shift of the stroke workend-diastolic volume relation or whether the slope of the relation also increased. Qualitative observation suggested, however, that the slope of the relation did increase with higher grades of pulmonary arterial occlusion (Figures 2 and 3). For the same reasons, it was not possible to quantify the end-systolic pressure-volume relation during steady-state pulmonary arterial occlusion by linear regression analysis. Nevertheless, it is clear that the increase in left ventricular transmural systolic pressure and stroke volume from a given end-diastolic volume during pulmonary arterial occlusion indicates an increase in the end-systolic pressure-volume ratio of the left ventricle (Figure 140 Circulation Research Vol 65, No 1, July 1989 4000 PAO Grade 1 PAO Grade 2 O o en I ' 0.997 Downloaded from http://circres.ahajournals.org/ by guest on June 18, 2017 LV END-DIASTOLIC VOLUME (ml) 70 50 LV END-DIASTOLIC VOLUME (ml) 4500 • PAO Grade 1 ° PAO Grade 2 o o r- 0.950 70 LV END-DIASTOLIC VOLUME (ml) FIGURE 3. Mean developed left ventricular (LV) ejection pressure (A) and left ventricular stroke volume (B) plotted against end-diastolic volume for the same vena caval occlusion (VCO) and pulmonary arterial occlusion (PAO) shown in Figure 4. Both the ejection pressure and stroke volume increase with pulmonary arterial occlusion. 2). This observation is consistent with the leftward shift of the left ventricular end-systolic pressurevolume relation observed in isolated hearts when right ventricular volume was increased, i3-24-39 Left ventricular systolic pressure has been observed previously to increase after sudden constriction of the pulmonary artery during the preceding diastole.28 Although repeated determinations of the endsystolic pressure-volume relation have been shown recently to be subject to significant variability,40 this variability cannot account for the consistent, unidirectional shift (i.e., increase) in the end-systolic 0 B 50 LV E N D - D I A S T O L I C VOLUME ( m l ) FIGURE 4. Left ventricular (LV) stroke work-enddiastolic volume relations for mild and moderate grades of steady-state pulmonary arterial occlusion (PAO) in one dog (A) and for two severe grades of steady-state pulmonary arterial occlusion in another dog (B). The linear regression lines obtained during vena caval occlusion (VCO) are stiown for comparison. elastance of the left ventricle with increased right ventricular load. The augmentations in both stroke work aad the end-systolic pressure-volume ratio of the left ventricle with pulmonary arterial occlusion indicate improved left ventricular systolic performance. While increased autonomic tone might have contributed to this increased systolic performance, there was no significant change in heart rate during pulmonary arterial occlusion, and a similar increase in Feneley et al Systolic Ventricular Interaction 141 END-EJECTION END-DIASTOLE 60 FIGURE 5. The relation between the septal-free wall and the anteroposterioT left ventriccular minor axis dimensions at end diastole (A) and at end ejection (B) during vena caval occlusion (VCO) and pulmonary arterial occlusion (PAO) in one study. Both relations are shifted to the right during pulmonary arterial occlusion. 75 60 LV ANTERO-POSTERlOR DIMENSION (cm) Downloaded from http://circres.ahajournals.org/ by guest on June 18, 2017 left ventricular systolic performance was observed after autonomic blockade. The augmented left ventricular performance appears attributable predominantly, therefore, to the altered loading conditions during pulmonary arterial occlusion. The present experimental preparation, however, does not permit definite conclusions to be drawn concerning the mechanism of this ventricular interaction. Leftward systolic interventricular septal displacement due to right ventricular systolic hypertension increases the radius of septal curvature,31'33-35 which would tend to increase septal tension, but a previous study from this laboratory demonstrated in an identical experimental preparation that systolic septa] tension decreased during pulmonary arterial occlusion because the reduction in the left-to-right transseptal pressure gradient outweighed the increase in the radius of curvature.31 Moreover, because the mass of the interventricular septum is constant, leftward systolic septal displacement and enhanced septal shortening must be accompanied by increased septal thickening. The combination of decreased systolic septal tension and increased septal thickness during pulmonary arterial occlusion implies a reduction in systolic septal stress (i.e., TABLE 1. 75 septal afterload). On this basis, the increment in the work output from the left ventricular chamber during pulmonary arterial occlusion could be viewed as resulting, in some part, from the transduction of right ventricular energy expenditure to the services of the left ventricular chamber via the inter ventricular septum. The common muscle fiber pathways that invest both ventricles,41 however, could provide the primary mechanistic basis for this energy transfer. It is well recognized that the forces acting on the external surface of the left ventricle must be accounted for when assessing left ventricular myocardial performance, but this is usually done by subtracting the pericardial pressure (or the intrapleural pressure) from the left ventricular chamber pressure, yielding free wall transmural pressure. This approach fails to account for the much greater external pressure acting on the remaining one third of the left ventricular surface area during systole. In effect, it is falsely assumed that the right ventricular systolic pressure is equivalent to the pericardial pressure; that is, it is assumed that the transseptal pressure is equivalent to the free wall transmural pressure. Hemodynamic, Volume, and Dimension Data Peak Peak Peak RVTMP/ TSP/ Peak Peak SW (beats/ EDV TSP LVTMP LVTMP SV at* Aa b*. Ab Cb, A c db. Ad RVTMP LVTMP min) (ml) (10-3 erg) (mm Hg) (mm Hg) (mm Hg) (mm Hg) (mm Hg) (ml) (cm) (%) (cm) (*) (cm) (%) (cm) (*) HR VCO Mean 128.7 SEM 8.0 PAO Mean SEM 1,886 450 32.2 6.7 106.2 83.2 6.0 7.8 7.0 125.7 38.4 2,674 76.8 123.5 52.8 9.6 6.5 380 9.5 5.5 8.9 39.1 0.30 0.05 0.78 0.03 13.8 7.67 1.7 5.99 3.2 5.21 6.1 2.25 10.3 2.5 0.22 0.6 0.25 0.5 0.17 0.8 0.06 1.7 0.63 0.08 0.43 0.07 18.0 7.82 2.0 6.16 3.4 4.94 9.4 1.86 20.0 2.5 0.25 0.5 0.24 0.6 0.18 1.2 0.09 3.6 HR, heart rate; EDV, end-diastolic volume; SW, left ventriccular stroke work; RV, right ventriccular; LV, left ventriccular; TMP, free wall transmural pressure; TSP, transseptal pressure; SV, left ventriccular stroke volume; a, base-apex dimension; b, anteroposterior dimension; c, septal-free wall dimension; d, septal component of septal-free wall dimension; be, beginning ejection; A, fractional systolic shortening; VCO, vena caval occlusion; PAO, pulmonary arterial occlusion. All statistical comparisons between the two occlusion states were significant (p<0.05), with the exception of HR, EDV, Aa, and Ab. 142 Circulation Research Vol 65, No 1, July 1989 weighted average of the right ventricular pressure {?„) and the pericardial pressure (Pp^) using the proportion of the external surface area of the left ventricle on which these pressures act as the weighting term,42 so that 150 E PRESSUR . a m O TRANSMURAL D a D P«t=(Sivs/Slv) • (6) VC0° •z. o O 1— JJ o O O —} UJ MEAN vco° TRANSSEPTAL • • * * _i A VI 45 LV END-DIASTOUC VOLUME (ml) Downloaded from http://circres.ahajournals.org/ by guest on June 18, 2017 END-EJECTION LV TRANSSEPTAL PRESSURE END- LV EJECTION TRANSSEPTAL PRESSURE ° 95 FIGURE 6. Panel A: Illustration of the differing effects of pulmonary arterial occlusion on the mean ejection left ventricular transseptal and free wall transmural pressures when compared with vena caval occlusion (VCO) over the same range of end-diastolic volumes. Panel B: End-ejection relation between the ratio of the septal and free wall components of the left ventricular septal-free wall dimension and the ratio of the transseptal and transmuralpressures during VCO and pulmonary arterial occlusion (PAO), over the same range of end-diastolic volumes. The dimension and pressure ratios are related linearly when the pressure ratio is low, but the dimension ratio approaches an upper limit as the pressure ratio approaches unity. In broad terms, there are two ways to account for the forces external to the entire left ventricular surface. One approach is to use modeling procedures to normalize the nonuniform external pressures. The simplest of these procedures is to calculate an effective external pressure (P m ) as the where S^ is the surface area of the right side of the interventricular septum and SK, is the total external surface area of the left ventricle. The assumption inherent in Equation 6 is that the compliance of the interventricular septum is identical to that of the left ventricular free wall. Little and coworkers demonstrated that this assumption is incorrect. They found that at end diastole, when the ventricle may be modeled as a passive structure, the ratio of the change in left ventricular pressure (Ph,) for a given change in P^ (APh/AP^) averaged 0.43 during vena caval occlusion, while the S,JS^ ratio averaged 0.33. Moreover, after interventricular septal hypertrophy was induced by pulmonary artery banding, the average S^SK, ratio increased to 0.38, but the average AP^/AP^ ratio declined to 0.21, indicating diminished septal compliance. The effects of vena caval and pulmonary arterial occlusions on the mean ejection left ventricular transseptal and free wall transmural pressures are illustrated over the same range of end-diastolic volumes in Figure 6A. If the systolic compliance of the interventricular septum were equal or proportionate to the compliance of the free wall, then a proportionate relation should exist between the ratio of the septal (d) and free wall (b/2) components of the left ventricular septal-free wall dimension (Equation 3), on one hand, and the ratio of the transseptal pressure and the transmural pressure, on the other. That this is not the case is illustrated in Figure 6B, where the end-systolic septal/free wall dimension ratio is plotted against the endsystolic transseptal/transmural pressure ratio for cardiac cycles during vena caval and pulmonary arterial occlusions over the same range of enddiastolic volumes. A linear relation exists between the dimension and pressure ratios when the pressure ratio is low (during pulmonary arterial occlusion), but the dimension ratio asymptotically approaches an upper limit, which is appreciably less than unity, when the pressure ratio is high (during vena caval occlusion). This relation indicates that the compliance of the interventricular septum diminishes abruptly as the transseptal pressure approaches the free wall transmural pressure and is compatible with evidence that when the transseptal and free wall transmural pressures are equal, the radius of curvature of the septum is considerably greater than that of the free wall.43 Septal compliance increases as the septum is shifted, thus explaining the progressive, beat-to-beat leftward shift of the stroke work-end-diastolic volume relation observed after abrupt pulmonary arterial occlusion, until the end- Feneley et al Systolic Ventricular Interaction Downloaded from http://circres.ahajournals.org/ by guest on June 18, 2017 diastolic volumes of the two ventricles approached a new steady state. This phenomenon explains the very recent observation that left ventricular performance increased only slightly during the first systole after diastolic pulmonary arterial occlusion,44 since the diastolic position of the septum had not yet changed. The dynamic variation in septal compliance with variation in the transseptal/transmural pressure ratio precludes the use of simple weighting functions, such as Equation 6, to normalize the nonuniform left ventricular external pressures. An alternative approach to this problem is to create experimental conditions in which the right ventricular pressure is made to approximate the pressure external to the left ventricular free wall. This approach is possible in isolated heart preparations, in which the right ventricle can be surgically opened to the ambient pressure and drained continuously, but is not applicable to studies of the intact circulation. One of the advantages of the vena caval occlusion technique as a method for assessing left ventricular performance in the intact subject is that this technique produces a rapid reduction in right ventricular volume and pressure, which precedes the reduction in left ventricular volume and pressure, thereby reducing the interactive contribution of the right ventricle to left ventricular function.31 A third approach, which has not been explored thus far, would be to express ventricular interaction directly in terms of biventricular energetics. In addition to the direct interactive effect of reduced left ventricular diastolic compliance, the reduced left ventricular preload during pulmonary arterial occlusion results from the "in series" effect of reduced right ventricular stroke volume, despite increased right ventricular end-diastolic volume. Consequently, the energy cost of the leftward displacement work performed on the interventricular septum and the increased external work output from the left ventricular chamber during pulmonary arterial occlusion could be expressed in terms of the reduction in the external work output from the right ventricular chamber for a given right ventricular preload. At present, the limitation to the quantitative development of such a model is the lack of an accurate method for determining the absolute right ventricular volume and, thus, the right ventricular stroke work-preload relation, during acute perturbations of loading conditions. Any such energetic model would have to account also for the effects of altered loading conditions on the mechanical efficiency of both ventricles. The observations made in this study pertain to an acute increase in right ventricular afterload. During chronic right ventricular pressure overload, hypertrophy of the interventricular septum might be expected to reduce the impact of direct ventricular interaction on left ventricular systolic function.38 Moreover, even under acute conditions, the pri- 143 mary effect of increased right ventricular afterload on left ventricular function is to cause a reduction in left ventricular preload, and thus stroke work and cardiac output. The present findings indicate, however, that the net reduction in stroke work in this situation is less than would be predicted by the reduction in preload. Finally, the important, coexistent effects of diastolic ventricular interaction with increased right ventricular afterload must not be overlooked; due to diminished left ventricular compliance, the increased end-diastolic pressure required to generate a given amount of stroke work2 may be the most important functional variable in some clinical situations. In summary, this study has implications concerning both systolic ventricular interaction and the impact of this interaction on the assessment of left ventricular systolic function. It demonstrates that at a given left ventricular end-diastolic volume, an acute increase in right ventricular systolic pressure increases the stroke work output from the left ventricular chamber. This increment in left ventricular stroke work represents energy transmitted to the left ventricle from the right ventricle. Current methods of assessing systolic left ventricular myocardial performance in vivo do not account for the nonuniform systolic transmural pressure of the ventricle. Consequently, these methods primarily reflect the net performance of the left ventricular chamber. This may be of little consequence in many situations. When comparing ventricular performance under conditions in which the relative hemodynamic load on either ventricle is altered, however, methods that account for energy transmission between the two ventricular chambers may be needed to accurately assess the myocardial performance of either ventricle. Acknowledgments The authors wish to gratefully acknowledge Ms. Barbara Lovell and Ms. Paula Poe for their expertise in manuscript preparation and editorial assistance. Appendix Tabulated below are experimental data demonstrating the reproducibility of repeated determinations of the left ventricular stroke workend-diastolic volume relation by linear regression analysis under constant loading conditions, in the presence and absence of autonomic blockade. The data were obtained for nine conscious dogs (18-30 kg). The methods of surgical instrumentation, data acquisition, and data analysis employed have been described in detail previously.32 Pharmacological autonomic blockade was achieved by administration of propranolol (1 mg/kg i.v.) and atropine (0.1 mg/kg i.v.). Linear regression data are presented for sequential pairs of vena caval occlusions (VCO). 144 Dog Circulation Research Vol 65, No 1, July 1989 Autonomic blockade Slope (erg • cm-3 • 103) VCO2 VC01 Jt-intercept (cm3) VCO1 VCO2 1 N 55 53 22 23 2 N 83 81 6 5 3 N 102 9 90 96 94 10 Y 6 6 N Y 101 80 92 24 24 32 33 N 57 82 54 8 7 Y 64 64 10 10 N 112 116 9 10 Y 102 96 11 N 63 12 13 14 26 4 5 6 Y 65 65 67 8 Y 56 51 18 26 15 9 Y 7 Downloaded from http://circres.ahajournals.org/ by guest on June 18, 2017 44 45 10 11 Mean 77 75 15 15 SEM 8 8 3 3 r VCO1 vco: 0.920 0.991 0.993 0.997 0.993 0.996 0.976 0.991 0.991 0.996 0.974 0.992 0.988 0.990 0.985 0.008 0.958 0.993 0.992 0.998 0.968 0.997 0.969 0.994 0.987 0.997 0.991 0.986 0.983 0.985 0.986 0.005 N, no; Y, yes; VCO, vena caval occlusion; r, linear correlation coefficient. References 1. Henderson Y, Prince AL: The relative systolic discharges of the right and left ventricles and their bearing on pulmonary congestion and depletion. Heart 1914;5:217-226 2. Moulopoulos SD, Sarcas A, Stamatelopoulos S, Arealis E: Left ventricular performance during by-pass or distension of the right ventricle. Ore Res 1965; 17:484-491 3. Taylor RR, Covell JW, Sonnenblick EH, Ross J Jr: Dependence of ventricular distensibility on filling of the opposite ventricle. AmJ Physiol 1967;213:711-718 4. Laks MM, Garner D, Swan HJC: Volumes and compliances measured simultaneously in the right and left ventricles of the dog. Ore Res 1967;20:565-569 5. Ludbrook PA, Byrne JD, McKnight RC: Influence of right ventricular haemodynamics on left ventricular pressurevolume relations in man. Circulation 1979;59:21-31 6. Elzinga G, van Grondelle R, Westerhof N, van den Bos GC: Ventricular interference. Am J Physiol 1974;226:941-947 7. Santamore WP, Lynch JR, Meier G, Heckman J, Bove AA: Myocardial interaction between the ventricles. JAppl Physiol 1976;41:362-368 8. Bemis CE, Serur JR, Borkenhagen D, Sonnenblick EH, Urschel CW: Influence of right ventricular filling pressure on left ventricular pressure and dimension. Ore Res 1974; 34:498-504 9. Tanaka H, Tei C, Nakao S, Tahara M, Sakurai S, Kashima T, Kanehisa T: Diastolic bulging of the interventricular septum toward the left ventricle. Circulation 1980;62:558-563 10. Brinker JA, Weiss JL, Lappe DL, Rabson JL, Summer WR, Permutt S, Weisfeldt ML: Leftward septal displacement during right ventricular loading in man. Circulation 1980; 61:626-633 11. Guzman PA, Maughan WL, Yin FCP, Eaton LW, Brinker JA, Weisfeldt ML, Weiss JL: Transseptal pressure gradient with leftward septal displacement during the Mueller manoeuvre in man. Br Heart J 1981;46:657-662 12. Kingma I, Tyberg JV, Smith ER: Effects of diastolic transseplai pressure gradient on ventricular septal position and motion. Circulation 1983;68:1304-1314 13. Janiclri JS, Weber KT: The pericardium and ventricular interaction, -distensibility, and function. Am J Physiol 1980; 238:H494-H503 14. Glantz SA, Misbach GA, Moores WY, Mathey DG, Levken J, Stowe DF, Parmley WW, Tyberg JV: The pericardium substantially affects the left ventricular diastolic pressurevolume relationship in the dog. Ore Res 1978;42:433-441 15. Bove AA, Santamore WP: Ventricular interdependence. Prog Cardiovasc Dis 1981;23:365-388 16 Starr I, Jeffers WA, Meade RH: The absence of conspicuous increments of venous pressure after severe damage to the right ventricle of the dog, with a discussion of the relation between clinical congestive failure and heart disease. Am Heart J 1943;26:291-301 17. Bakos ACP: The question of the function of the right ventricular myocardium: An experimental study. Circulation 1950;l:724-732 18. Kagan A: Dynamic responses of the right ventricle following extensive damage by cauterization. Circulation 1952; 5:816-823 19. Donald DE, Essex HE: Pressure studies after inactivation of the major portion of the canine right ventricle. Am J Physiol 1954;176:155-161 20. Oboler AA, Keefe JF, Gaasch WH, Banas JS Jr, Levine HJ: Influence of left ventricular isovolumic pressure upon right ventricular pressure transients. Cardiology 1973;58:32-44 21. Sawatani S, Mandell C, d Kusaba E: Ventricular performance following ablation and prosthetic replacement of right ventricular myocardium. Trans Am Soc Artif Intern Organs 1974;20:629-636 22. Seki S, Ohba O, Tanizaki M, Takahashi S, Teramoto S, Sunada T: Construction of a new right ventricle on the epicardium: A possible correction for underdevelopment of therightventricle. J Thorac Cardiovasc Surg 1975;7O:33O-337 23. Santamore WP: Mechanical interactions between the left and right ventricles (thesis). Philadelphia, Pa, Temple University, 1975 24. Weber KT, Janicki JS, Shroff S, Fishman AP: Contractile mechanics and interaction of the right and left ventricles. Am JCardiol 1981 ;47:686-695 25. Feneley MP, Gavaghan TP, Baron DW, Branson JA, Roy PR, Morgan JJ: Contribution of left ventricular contraction to the generation of right ventricular systolic pressure in the human heart. Circulation 1985;71:473-480 26. Elzinga G, Piene H, de Jong JP: Left and right ventricular pump function and consequences of having two pumps in one heart: A study on the isolated cat heart. Circ Res 1980; 46:564-574 27. Kelly DT, Spotnitz HM, Beiser GD, Pierce JE, Epstein SE: Effects of chronic right ventricular volume and pressure loading on left ventricular performance. Circulation 1971; 42:433-441 Feneley et al Downloaded from http://circres.ahajournals.org/ by guest on June 18, 2017 28. Langille BL, Jones DR: Mechanical interactions between the ventricles during systole. Can JPhysiol Pharmacol 1977; 55:373-382 29. Robotham JL, Mitzner W: A model of the effects of respiration on left ventricular performance. JAppl Physiol 1979; 46:411-418 30. Visner MS, Arentzen CE, O'Connor MJ, Larson EV, Anderson RW: Alterations in left ventricular three-dimensional dynamic geometry and systolic function during acute right ventricular hypertension in the conscious dog. Circulation 1983;67:353-365 31. Olsen CO, Tyson GS, Maier GW, Spratt JA, Davis JW, Rankin JS: Dynamic ventricular interaction in the conscious dog. Ore Res 1983;52:85-104 32. Glower DD, Spratt JA, Snow ND, Kabas JS, Davis JW, Olsen CO, Tyson GS, Sabiston DC Jr, Rankin JS: Linearity of the Frank-Starling relationship in the intact heart: The concept of preload recruitable stroke work. Circulation 1985;71:994-1009 33. King ME, Braun H, Goldblatt A, Liberthson R, Weyman AE: Interventricular septal configuration as a predictor of right ventricular systolic hypertension in children: A crosssectional echocardiographic study. Circulation 1983;68:68-75 34. Shimada R, Takeshita A, Nakamura M: Non-invasive assessment of right ventricular systolic pressure in atrial septal defect: Analysis of the end-systolic configuration of the ventricular septum by two-dimensional cchocardiography. AmJCardiol 1984;53:1117-1123 35. Feneley M, Gavaghan T: Paradoxical and pseudoparadowcal interventricular septal motion in patients with right ventricular volume overload. Circulation 1986;74:230-238 36. Tyson GS Jr, Maier GW, Olsen CO, Davis JW, Rankin JS: Pericardial influences on ventricular filling in the conscious dog: An analysis based on pericardial pressure. Ore Res 1984^4:173-184 Systolic Ventricular Interaction 145 37. Olsen CO, Tyson GS, Maier GW, Davis JW, Rankin JS: Diminished stroke volume during inspiration: A reverse thoracic pump. Circulation 1985;72:668-679 38. JJttle WC, Badke FR, O'Rourke RA: Effect of right ventricular pressure on end-diastolic left ventricular pressurevolume relationship before and after chronic right ventricular pressure overload in dogs without pericardia. Ore Res 1984;54:719-730 39. Maughan WL, Kallman CH, Shoukas A: The effect of right ventricular filling on the pressure-volume relationship of the ejecting canine left ventricle. Ore Res 1981;49:382-388 40. Spratt JA, Tyson GS, Glower DD, Davis JW, Muhlbaier LH, Olsen CO, Rankin JS: The end-systolic pressurevolume relationship in conscious dogs. Circulation 1987; 75:1295-1309 41. Streeter DD Jr: Gross morphology and fiber geometry of the heart, in Berne RM (ed): Handbook of Physiology, Section 2. Bethesda, Md, American Physiology Society, 1979, pp 66-68 42. Mirsky I, Rankin JS: The effects of geometry, elasticity, and external pressures on the diastolic pressure-volume and stiffness-stress relations: How important is the pericardium? Ore Res 1979;44:601-611 43. Lima JAC, Guzman PA, Yin FCP, Brawley RK, Humphrey L, Traill TA, Lima SD, Marino P, Weisfeldt ML, Weiss JL: Septal geometry in the unloaded living human heart. Circulation 1986;74:463-468 44. Slinker BK, Goto Y, LeWinter MM: Direct systolic ventricular interaction affects left ventricular contraction and relaxation (abstract). Circulation 1987;76(suppl IV):IV-427 KEY WORDS interaction ventricular interdependence • ventricular Effect of acutely increased right ventricular afterload on work output from the left ventricle in conscious dogs. Systolic ventricular interaction. M P Feneley, C O Olsen, D D Glower and J S Rankin Downloaded from http://circres.ahajournals.org/ by guest on June 18, 2017 Circ Res. 1989;65:135-145 doi: 10.1161/01.RES.65.1.135 Circulation Research is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 1989 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7330. Online ISSN: 1524-4571 The online version of this article, along with updated information and services, is located on the World Wide Web at: http://circres.ahajournals.org/content/65/1/135 Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Circulation Research can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Circulation Research is online at: http://circres.ahajournals.org//subscriptions/