Linearity of the left ventricular end-systolic pressure-volume relation in patients with severe heart failure

The left ventricular end-systolic pressure-volume relation is a relatively load-independent measure of left ventricular contractile function. Linearity of the relation derived from full left ventricular pressure-volume loops has not previously been demonstrated for patients with severe heart failure. Therefore, nine patients with markedly depressed left ventricular systolic function (ejection fraction 0.14 +/- 0.08) were studied with micromanometer left ventricular pressure measurement and simultaneous radionuclide ventriculography. Afterload was reduced with graded infusions of nitroprusside, allowing construction of pressure-volume loops under four afterload conditions in four patients and three afterload conditions in the other five patients. The end-systolic pressure-volume relation derived from the pressure-volume loops was found to be linear for the range of pressures and volumes examined, with correlation coefficients in individual patients ranging from 0.936 to 0.999 (mean 0.981). The mean slope of the relation (or end-systolic elastance) was 0.71 mm Hg/ml (range 0.42 to 1.52), and the extrapolated volume intercept at zero pressure was positive in all patients. An exponential relation between end-systolic elastance and ejection fraction was demonstrated for this group of patients. Approximations of end-systolic elastance obtained from measurements other than the full pressure-volume loops correlated variably with "true" elastance obtained from the pressure-volume loops. The relation between stroke work and end-diastolic volume was nonlinear in most patients. Thus, the end-systolic pressure-volume relation is linear in the "physiologic" range in patients with severe heart failure. This finding should permit construction of the relation from two loading conditions in clinical studies, facilitating its use as an index of contractile function in patients with heart failure.     

Disparity between ejection and end-systolic indexes of left ventricular contractility in mitral regurgitation

To examine left ventricular function in mitral regurgitation (MR), we compared the ejection phase indexes of left ventricular contractility with maximal systolic elastance (Emax) in an experimental preparation of MR. In eight anesthetized open-chest dogs, pressure-volume loops were derived during afterload manipulation with methoxamine and nitroprusside from simultaneous left ventricular pressure and dimensional (sonomicrometry techniques) data before and after creation of MR. From these data maximal systolic elastance (Emax), the end-systolic pressure-volume relationship (ESPVR), and the end-systolic stress-volume relationship (ESSVR) were determined by linear regression analysis. After creation of MR, end-diastolic volume increased significantly (40 +/- 13 to 53 +/- 18 ml, p less than .001); likewise end-systolic volume increased (28 +/- 11 to 33 +/- 15 ml, p less than .05). Ejection fraction increased after MR (35 +/- 6% to 44 +/- 8%, p less than .005), as did the mean velocity of fiber shortening (0.62 +/- 0.20 to 1.02 +/- 0.39 sec-1, p less than .02). In contrast, Emax declined significantly (4.63 +/- 2.5 to 3.54 +/- 1.94 mm Hg/ml, p less than .05); ESPVR and ESSVR showed similar directional changes. An inverse relationship was found between systolic elastance and end-diastolic volume in both control and MR states. When Emax, ESPVR, and ESSVR were normalized to end-diastolic volume, they were unchanged after MR. These results suggest that either there was a decline in left ventricular contractile state after MR, or that contractility was unchanged (if elastance is normalized for increased contractility, but occurred as a consequence of increased preload with no significant change in afterload.     

Effect of dobutamine on ventriculo-arterial coupling and ventricular work efficiency in patients with cardiac failure

In nine patients with cardiac dysfunction (ejection fraction less than or equal to 50%), we evaluated the effects of dobutamine (5 micrograms/kg/min) on ventriculo-arterial coupling by monitoring direct arterial pressures and simultaneously-recorded M-mode echocardiograms guided with two-dimensional images. Left ventricular end-diastolic volume (EDV) and end-systolic volume (ESV) were calculated by the formula of Teichholz, and left ventricular end-systolic pressure (ESP) was approximately from the arterial dicrotic pressure. Arterial pressure was altered by phenylephrine or nitroprusside and the slope (Ees) and volume axis intercept (Vo) of the end-systolic pressure-volume relationship were determined as the contractile properties of the ventricle. The arterial system properties were expressed by the slope (Ea) of the end-systolic pressure-stroke volume relationships. Ees during dobutamine infusion was derived assuming that the Vo was unchanged from the baseline state. The left ventricular pressure-volume area (PVA), the sum of external work (EW) and end-systolic potential energy (PE), and ventricular work efficiency (EW/PVA) were determined from a time-varying elastance model. The EDV and ESV were significantly decreased by dobutamine (-4%, p less than 0.05; -22%, p less than 0.01), while the ESP and heart rate remained unchanged. Dobutamine increased the Ees markedly (+41%, p less than 0.01) and decreased the Ea (-23%, p less than 0.01). These changes resulted in a substantial decrease in the ratio of Ea to Ees (-44%, p less than 0.01). The EW was augmented (+22%, p less than 0.01), but the PE was reduced (-33%, p less than 0.01) by dobutamine, while the PVA remained the same as in the baseline state.(ABSTRACT TRUNCATED AT 250 WORDS)     

The relationship of various measures of end-systole to left ventricular maximum time-varying elastance in man

This investigation was designed to calculate left ventricular maximum time-varying elastance (Emax), to define the relationship between Emax and pressure-volume (P-V) relations at other, more easily defined measured of end-systole, and to determine whether these measures of left ventricular contractile function can be normalized in man. Accordingly, we studied 10 subjects with simultaneous high-fidelity micromanometer left ventricular and ascending aortic pressure recordings and biplane contrast cineangiograms at control conditions and during infusion of methoxamine and nitroprusside. Emax was defined as the maximum slope of the linear relation of isochronal, instantaneous P-V data points obtained from each of the three loading conditions. Left ventricular end-systole was also defined for each loading condition as: the time of the maximum P-V ratio (maxPV), minimum ventricular volume (minPV), (-)dP/dtmin [(-)dP/dtPV], and zero systolic flow approximated by the central aortic dicrotic notch (AodiPV). The mean heart rates and LV (+)dP/dtmax were insignificantly altered during the three loading conditions. Isochronal Emax ranged from 3.38 to 6.73 mm Hg/ml (mean 5.48 +/- 1.23 [SD] mm Hg/ml) and the volume-axis intercepts at zero pressure ranged from -2 to 51 ml (mean 18 +/- 16 ml). The isochronal slope calculations were reproducible (r = .97 to .99). The end-systolic P-V slope values for the maxPV, minPV, (-)dP/dtPV, and AodiPV relations correlated with isochronal Emax (r = .90, .88, .69, and .74, respectively). The average slope values for these end-systolic P-V relations, however, underestimated the mean Emax (p less than .01 to p less than .001). The mean extrapolated volume-axis intercepts for these end-systolic P-V relations also underestimated that for Emax. Finally, the isochronal Emax and other end-systolic P-V relation slope values demonstrated inverse linear relationships with left ventricular mass (r = -.68 to -.91, p less than .05 to p less than .001). Only the Emax volume-axis intercepts showed a linear relationship with left ventricular end-diastolic volume (r = .75). Thus we conclude that the time-varying elastic properties of the left ventricle can be calculated in man, that commonly used end-systolic P-V relations significantly underestimate isochronal Emax, and that normalization of isochronal Emax and other end-systolic P-V relation slope values might be performed in man with left ventricular mass; no obvious relationship between volume-axis intercepts and measures of left ventricular or body size was apparent.     

Measurement of end-systolic pressure-volume relations by intra-aortic balloon occlusion

A new situ technique has been developed for measuring peak end-systolic elastance, Emax, that does not alter intrinsic or reflex-stimulated cardiac contractility. Afterload is varied by the inflation of an intra-aortic balloon catheter positioned in the ascending aorta. Balloon inflation is timed to interrupt ventricular ejection transiently at different times during the ejection phase, therefore, producing contraction at different ventricular volumes. Simultaneous measurement of left ventricular pressure and aortic flow during the occlusion sequence allows pressure versus ejected volume loops to be generated, from which the end-systolic pressure-volume relation is determined. End-systolic pressure-volume relation (ESPVR) was measured in six anesthetized Dorsett sheep with normal and enhanced contractile states. ESPVR was analyzed using both linear and nonlinear techniques. Although nonlinear components were seen in ESPVR, for the pressure-volume data range produced by the transient occlusions, linear approximations of ESPVR fit the end-systolic data points well. In the normal state, Emax, the slope of the linear ESPVR, was 1.01-5.08 mm Hg/ml in animals with body weights of 23-32 kg. After epinephrine infusion, Emax increased from 3.07 +/- 1.49 to 5.79 +/- 1.97 mm Hg/ml, which is consistent with previous investigations. Linear and nonlinear volume intercepts had a small increase with positive inotropic stimulation. Furthermore, serial measurements of Emax tracked cardiac function in depressed hearts with rapidly changing contractility.     

Assessment of the end-systolic pressure-volume relationship in human beings with the use of a time-varying elastance model

The analysis of left ventricular end-systolic pressure-volume relationships in human beings has been hindered by the lack of a practical method of serial volume assessment and by an imprecise definition of end-systole. Modifications of the end-systolic relationship that have been used to circumvent these problems have included the use of single-point end-systolic pressure-volume ratios, the use of peak systolic pressure/minimum ventricular volume points for end-systolic points, and the use of end-ejection as a marker for end-systole. To assess the correlation between the parameters generated by these modifications with the slope (Emax) and volume intercept (VO) of the end-systolic line as defined by Sagawa's model of time-varying elastance, simultaneous measurement of left ventricular pressure and gated radionuclide volume was made in 26 patients under various loading conditions and pressure-volume diagrams were constructed for each loading condition from 32 simultaneous pressure-volume coordinates. Two pressure-volume diagrams were recorded in 14 patients and three pressure-volume diagrams were recorded in 12 patients. Emax and VO were determined in all patients from the slope and volume intercept of the isochronic pressure-volume line with the maximum time-varying elastance as described by Sagawa's model and were designated true Emax and true VO, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Application of a time varying elastance model to right ventricular performance in man

To evaluate instantaneous right ventricular pressure-volume relations we studied nine patients with normal coronary anatomy and ventricular function with simultaneous high fidelity pressure, flow-velocity, and biplane cineventriculographic volumes (60 frames.s-1) during atrial pacing at 93(SD5) beats-min-1, partial autonomic blockade, and pharmacologically altered ventricular loading. The maximum time varying elastance, Emax, was defined as the maximum slope of isochronal, simultaneous pressure-volume data points derived by linear regression analysis from three loading conditions. The slope of the non-isochronal maximum pressure/volume ratio, pressure at minimum volume, end ejection pressure/volume, and peak right ventricular pressure/minimum volume were also derived from the three loading conditions. The mean slope for Emax was 1.30(0.84) mm Hg.ml-1 (range 0.62-2.87) and the volume axis intercept at zero pressure (Vo) was 46(21) ml (range 24-89 ml). Time dependent Emax was characterised by a series of parallel shifting lines of best fit with large changes in Vo in addition to changes in the slope of the pressure volume relations. Only maximum pressure/volume ratio and peak pressure/minimum volume were linearly related to Emax (r = 0.82 and 0.84 respectively, p = 0.05) while pressure at minimum volume and end ejection pressure/volume did not correlate with Emax. We conclude that in normal human subjects (1) right ventricular systolic function may be approximated using a time varying elastance model characterised by a time dependent Vo; (2) end systolic pressure-volume relations using maximum pressure/volume ratio and peak pressure/minimum volume systematically estimate Emax; and (3) other right ventricular end systolic pressure-volume relations near end ejection bear no obvious relation to Emax because of the wide temporal separation between peak systolic elastance and end ejection in this chamber.     

The left ventricular dP/dtmax-end-diastolic volume relation in closed-chest dogs

I investigated the relation of the maximum rate of left ventricular pressure rise to the end-diastolic volume and the comparison of the maximum rate of left ventricular pressure rise-end-diastolic volume relation to the end-systolic pressure-volume relation, using the time-varying elastance model. These studies were performed in 11 dogs chronically instrumented to measure left ventricular pressure and determine left ventricular volume from three orthogonal dimensions. During vena caval occlusions, the relations between the maximum rate of left ventricular pressure rise and end-diastolic volume were described by straight lines (r = 0.97 +/- 0.01, mean +/- SD). Dobutamine increased the slope of the maximum rate of left ventricular pressure rise-end-diastolic volume relation to 358 +/- 94% of control. This increase was greater than the 244 +/- 61% increase in the slope of the end-systolic pressure-volume relation (P less than 0.005). The volume intercepts of the maximum rate of left ventricular pressure rise-end-diastolic volume relation and end-systolic pressure-volume relation were similar and were not significantly altered by dobutamine. The ratio of the slope of the maximum rate of left ventricular pressure rise-end-diastolic volume relation to the slope of the end-systolic pressure-volume relation divided by the time from end-diastole to end-systole was similar before (2.2 +/- 0.7) and after dobutamine (2.3 +/- 0.7, P = NS). Angiotensin II did not significantly alter the maximum rate of left ventricular pressure rise-end-diastolic volume relation generated by caval occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Simultaneous determination of left ventricular end-systolic pressure-volume and pressure-dimension relationships in closed-chest dogs

The left ventricular end-systolic pressure-volume relationship is a load-insensitive measure of left ventricular performance. The relationship at end-systole between left ventricular pressure and dimension is more easily obtained, but the conflicting results of previous studies make it unclear if it has the same properties as the left ventricular end-systolic pressure-volume relationship. To address this issue, 11 dogs were instrumented to measure left ventricular pressure and three orthogonal left ventricular dimensions. Left ventricular pressure and dimensions were varied by use of caval occlusion. Left ventricular volume was calculated as an ellipsoid. The left ventricular end-systolic pressure-volume relationship and each of the three end-systolic pressure-dimension relations were described by straight lines (r = .97 +/- .02, mean +/- SD). In six animals, dobutamine produced similar significant increases (p less than .01) in the slope of the end-systolic pressure-volume relationship (244 +/- 61% of control), the end-systolic pressure-anterior-posterior dimension relationship (248 +/- 89%), the end-systolic pressure--septal-lateral dimension relationship (211 +/- 95%), and the end-systolic pressure-basal-apical dimension relationship (210 +/- 85%). The intercepts at zero pressure were relatively unchanged by dobutamine. In contrast, occlusion of the distal left anterior descending coronary artery in five animals produced a rightward shift of the left ventricular end-systolic pressure-volume relationship and the pressure--basal-apical dimension relationship, while the pressure--anterior-posterior dimension and pressure--septal-lateral dimension relationships were relatively unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inotropic effect of enoximone in patients with severe heart failure: demonstration by left ventricular end-systolic pressure-volume analysis

Left ventricular end-systolic pressure-volume analysis was employed to assess the inotropic effect of the phosphodiesterase inhibitor enoximone (formerly MDL-17,043) in nine patients with severe heart failure (New York Heart Association class IV symptoms, mean ejection fraction = 0.22). Left ventricular pressure-volume loops were constructed using high fidelity left ventricular pressure measured with micromanometer-tipped catheters and simultaneous left ventricular volume obtained by gated blood pool imaging. Afterload was reduced with the vasodilator nitroprusside to generate the baseline left ventricular end-systolic pressure-volume relation, a relatively load-independent measure of contractile function. The intravenous administration of enoximone (mean dose 75 mg) shifted the end-systolic pressure-volume point upward and leftward from the baseline pressure-volume relation in eight of the nine patients, demonstrating a positive inotropic effect of this agent. The maximal rate of left ventricular pressure development (peak positive dP/dt) increased from 1,030 +/- 142 to 1,381 +/- 219 mm Hg/s (p less than 0.01) on enoximone despite a significant decrease in preload (as assessed by left ventricular end-diastolic pressure and volume) and a small, insignificant decrease in mean arterial pressure. Two patients developed angina after enoximone administration; both patients had coronary artery disease and experienced a greater than 30% increase in heart rate-systolic blood pressure product. Thus, enoximone has a significant inotropic effect in patients with severe heart failure. Like other inotropic drugs, it has the potential to increase myocardial oxygen demand and thereby precipitate ischemia.     

Left ventricular function in coronary artery disease. Evaluation of slope of end-systolic pressure-volume line (Emax) and ratio of peak systolic pressure to end-systolic volume (P/Ves)

Left ventricular function was assessed by measurement of systolic pressure-volume variables and ejection fraction in seven normal subjects (group I), five patients with coronary artery disease and normal symmetric left ventricular wall motion (group II) and eight patients with remote myocardial infarction and segmental akinesia (group III). Left ventricular volumes were obtained from right anterior oblique ventriculograms and pressures from catheter-tip micromanometer (14 patients) or fluid-filled catheters (6 patients) at two different systolic loads. P/Ves was calculated as the ratio of peak systolic pressure (P) to end-systolic volume (Ves) at rest, Emax as the slope of the end-systolic pressure volume line constructed at two systolic loads, and Vo as the volume axis intercept of this line. Emax was significantly (p less than 0.01) lower in patients with segmental akinesia (group III) (5.0 +/- 0.5) than in normal subjects (group I) (10.4 +/- 0.8) or patients with coronary artery disease and normal wall motion (group II) (9.9 +/- 0.8). In contrast, there was no significant difference in P/Ves among the three groups (6 +/- 1.0 in group I, 5 +/- 0.8 in group II, 3.7 +/- 0.5 in group III). Similarly, Ves and Vo failed to separate the three groups. Although ejection fraction was significantly (p less than 0.05) lower in group III (0.56 +/- 0.03) than in groups I and II (0.67 +/- 0.03 in both groups), there was considerable overlap of individual values in the three groups. In eight patients, measurements were repeated during isometric exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute respiratory acidosis decreases left ventricular contractility but increases cardiac output in dogs

To understand the cardiovascular response to respiratory acidosis, we measured hemodynamics, left ventricular pressure, and left ventricular volume (three ultrasonic crystal pairs) during eucapnia and respiratory acidosis in 10 fentanyl-anesthetized open-chest dogs. Left ventricular contractility was assessed primarily by measuring the slope (Emax) and intercept (V0) of the left ventricular end-systolic pressure-volume relation determined by combining end-systolic points from a vena caval occlusion and from brief aortic cross-clamping. Respiratory acidosis (pH 7.09, Pco2 92 mm Hg) reduced contractility by a decrease in Emax (11.4 to 9.2 mm Hg/ml, p less than 0.01) with no change in V0. Despite this, cardiac output increased (1.7 to 2.1 l/min, p less than 0.01), and heart rate increased (96 to 121 beats/min, p less than 0.05), with no change in blood pressure. Systemic vascular resistance fell by 26% (p less than 0.01). During eucapnia, propranolol reduced Emax (11.4 to 4.6 mm Hg/ml, p less than 0.01) with no change in V0. After propranolol treatment, respiratory acidosis further reduced Emax (4.6 to 3.6 mm Hg/ml, p less than 0.05) and increased end-systolic volume more than before propranolol (p less than 0.001). Now cardiac output did not increase even though heart rate increased (81 to 106 beats/min, p less than 0.001) and systemic vascular resistance fell by 20% (p less than 0.01). We conclude that the effect of respiratory acidosis on the circulation is to increase venous return (equals cardiac output) in the face of decreased left ventricular contractility. The beta-adrenergic response to respiratory acidosis substantially ameliorated the increase in end-systolic volume and supported the increase in venous return but did not alter the associated tachycardia or vasodilation. Respiratory acidosis, like propranolol treatment, decreases contractility by decreasing Emax.     

Evaluation of left ventricular contractile performance utilizing end-systolic pressure-volume relationships in conscious dogs

The relationship between left ventricular end-systolic pressure and volume has been proposed as a model of left ventricular contraction which may be useful for quantifying inotropic state independent of preload and afterload. Although the model has been well-validated in isolated hearts, systematic evaluation in conscious animals with an intact peripheral circulation has been limited. Accordingly, we derived end-systolic pressure-volume relationships in twelve conscious dogs, chronically instrumented to measure left ventricular pressure and dimensions from endocardial ultrasonic crystals in three orthogonal axes. We examined the linearity of the end-systolic pressure-volume relationship, its response to alterations of inotropic state and the peripheral circulation, and the influence of beta-adrenergic reflexes. End-systolic pressure-volume relationships were constructed by linear regression of end-systolic pressure-volume coordinates produced by transient inferior vena caval occlusions during atrial pacing. The relations were highly linear; of 127 inferior vena caval occlusions, the correlation coefficient was 0.96 +/- 0.05 (mean +/- SD). The slope of the end-systolic pressure-volume relationship was not significantly altered either by a moderate resistive afterload induced by angiotensin II infusion, or by a moderate increase in preload produced by dextran, but was increased from 4.7 +/- 2.3 to 6.5 +/- 2.2 mm Hg/ml (P less than 0.05) in response to the positive inotropic stimulus of dobutamine. The volume intercept at zero end-systolic pressure was unaffected by dextran or dobutamine, but was decreased from 12 +/- 8 to 5 +/- 11 ml (P less than 0.01) by angiotensin II infusion, indicating a leftward shift of the end-systolic pressure-volume relationship.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ventricular-load optimization by inotropic stimulation in patients with heart failure

To evaluate the effects of inotropic stimulation on ventriculo-arterial coupling, we determined both the slope of the end-systolic pressure-volume relationship (ventricular elastance) and the slope of end-systolic pressure-stroke volume relationship (arterial elastance) at rest and during dobutamine infusion (5 micrograms/kg/min). We also determined stroke work, end-systolic potential energy and the ventricular work efficiency defined as stroke work per pressure volume area (stroke work + potential energy). In the resting state, ventricular elastance was lower than arterial elastance and work efficiency was about 59.7 +/- 9.3% (mean +/- SD). This condition is remote from the point where stroke work or mechanical efficiency is optimal. Enhanced ventricular elastance by 41% with dobutamine resulted in a significant reduction in both left ventricular end-diastolic and end-systolic volumes and was accompanied by the reduction in arterial elastance by 23%. Consequently, the ratio of arterial elastance to ventricular elastance decreased from 1.43 +/- 0.57 to 0.82 +/- 0.47, which resulted in an increase in stroke work, a decrease in potential energy and hence a marked increase in work efficiency. Thus, inotropic stimulation of depressed hearts could modulate ventriculo-arterial coupling towards optimization of either stroke work or mechanical efficiency.     

The slope of the end-systolic pressure-volume relationship compared with the global end-systolic pressure-volume ratio in humans

The slope of the end-systolic pressure-volume relationship (Emax), which is generated clinically by load manipulation, as well as the "absolute" peak systolic pressure end-systolic volume ratio (denoted as pressure-volume ratio), have been suggested as indices defining left ventricular function. This study represents an attempt to determine the relationship between these two indices by studying 20 patients (16 with coronary artery disease and 4 with normal coronary arteries) undergoing cardiac catheterization. Left ventriculography was performed three times in each patient: (1) in the control baseline state, (2) after rapid intravenous infusion of 250-300 cc of saline, and (3) after sublingual administration of 5 mg isosorbide dinitrate. Emax was approximated by linear regression using the peak left ventricular pressure (replacing end-systolic pressure) and the smallest left ventricular (end-systolic) volume for these three different loads. Acute ischemia with typical chest pain and ECG changes developed in 4 patients during saline loading. The pressure-volume ratio showed no change with load manipulation in patients who did not demonstrate ischemia. In the 4 patients who developed acute ischemia, the pressure-volume ratio dropped from 4.4 +/- 1.3 to 2.9 +/- 0.9 mmHg/ml (p less than 0.001). In all of the patients, the pressure-volume ratio, but not the Emax, correlated with the ejection fraction (r = 0.6; p less than 0.05). In addition, the Emax line demonstrated a markedly nonphysiological Vo. There was no correlation between Emax and pressure-volume ratio.(ABSTRACT TRUNCATED AT 250 WORDS)     

Independence of left ventricular pressure-volume ratio from preload in man early after coronary artery bypass graft surgery

The response of the maximum value of the left ventricular pressure-volume ratio to preload augmentation by blood or plasma expanders was studied in 11 patients during the first 24 hr after coronary artery bypass graft surgery. Increasing the mean left atrial pressure from 10 to 15 and 20 mm Hg resulted in no change in the maximum pressure-volume ratio in the group as a whole. In certain individual patients, however, the maximum pressure-volume ratio changed with volume infusion, and these changes were accompanied by simultaneous changes in afterload. The observed changes in pressure-volume ratio were in the same direction as the changes in afterload (systolic pressure), suggesting a dependence of maximum pressure-volume ratio on afterload. These results show that the maximum pressure-volume ratio is independent of preload in the first 24 hr after coronary artery bypass graft surgery with the pericardium open; thus the maximum pressure-volume ratio is a useful index of postoperative left ventricular function when afterload is unchanged. However, because this ratio (a single-point assessment of the pressure-volume relationship) may not be a good estimate of Emax, we recommend a more complete determination of the locus of the "upper left corners" of the pressure-volume loops for measurement of Emax to provide a more accurate indicator of the myocardial contractile state.     

Responsiveness of the maximum time-varying elastance to alterations in left ventricular contractile state in man

This investigation was designed to establish the relative responsiveness of maximum time-varying elastance (Emax) slope values to alterations in left ventricular contractile state in comparison with isovolumic and ejection phase indices in man. Accordingly, nine patients had a bipolar right atrial pacing catheter and micromanometer left ventricular catheter placed and red blood cells tagged with technetium-99m for radionuclide angiography. Hemodynamic measurements and radionuclide angiograms were acquired simultaneously over a range of loading conditions produced by methoxamine or nitroprusside infusions during both the basal and enhanced contractile states. Enhanced left ventricular contractility was produced by a steady-state dobutamine infusion of 2 to 10 mu/kg/min. The mean (+)dP/dtmax increased from 1510 +/- 460 mm Hg/sec during the basal state to 2537 +/- 546 mm Hg/sec (p less than 0.001) during the dobutamine infusion. The mean Emax slope value also increased from 4.34 +/- 1.40 mm Hg/ml during the basal state to 6.41 +/- 1.90 mm Hg/ml (p less than 0.001) during the dobutamine infusion. The average percent change in the Emax slope value (51 +/- 26%) was less than those for the isovolumic indices (57% to 112%), while it was more than those for the ejection phase indices (11% to 53%). When the variability in the percent changes for each of these contractile indices was incorporated into the analysis, the Emax slope values demonstrated a greater responsiveness to changes in left ventricular contractility than did the isovolumic and ejection phase indices. In conclusion, the Emax slope value calculated by this method is a contractile index, which is less affected by measurement variability and the influences of loading conditions than are the isovolumic and ejection phase indices, and therefore may improve our ability to both detect and quantitate changes in left ventricular contractility in man.     

Comparison of preload recruitable stroke work, end-systolic pressure-volume and dP/dtmax-end-diastolic volume relations as indexes of left ventricular contractile performance in patients undergoing routine cardiac catheterization.

The end-systolic pressure-volume relation, the relation between stroke work and end-diastolic volume, termed the preload recruitable stroke work relation, and the relation between the peak of the first derivative of left ventricular pressure (dP/dtmax) and end-diastolic volume have been employed as linear indexes of left ventricular contractile performance in laboratory animals. The purpose of this study was to examine the relative utility of these indexes during routine cardiac catheterization in seven human subjects (mean age 48 +/- 18 [SD] years) with a normal left ventriculogram and coronary angiogram. Left ventricular pressure was recorded continuously with a micromanometer catheter, and left ventricular volume was derived from digital subtraction contrast ventriculograms obtained at 30-ms intervals. Transient occlusion of the inferior vena cava with a balloon-tipped catheter was employed to obtain beat to beat reductions in left ventricular pressure and volume over 8.7 +/- 1.7 cardiac cycles. Stroke work declined by 49 +/- 13% during vena caval occlusion, but end-systolic pressure fell by only 26 +/- 11%, and changes in dP/dtmax were small and inconsistent (12 +/- 22%). Consequently, the range of data available for determination of the preload recruitable stroke work relation greatly exceeded that for the end-systolic pressure-volume relation and the dP/dtmax-end-diastolic volume relation, and much less linear extrapolation from the measured data was required to determine the volume-axis intercept. Preload recruitable stroke work relations were highly linear (r = 0.95 +/- 0.07), and much more so than end-systolic pressure-volume relations (r = 0.79 +/- 0.23).(ABSTRACT TRUNCATED AT 250 WORDS)     

End-systolic pressure-volume relationships obtained by conductance catheter and transient inferior vena caval occlusion: their clinical usefulness]

Whether beneficial hemodynamic effects of cardiovascular drugs are due to changes in the inotropic or loading conditions has been difficult to determine in clinical settings. In this study, the end-systolic pressure-volume relationship, known as a load-independent measurement of cardiac contractility, was obtained by a volumetric conductance catheter and transient inferior vena caval occlusion. We applied this technique to determine the major mode of hemodynamic action of a new inotropic vasodilator, OPC-8490, in comparison to that of dobutamine. In 7 patients with anterior myocardial infarction, an 8F conductance catheter with pressure micromanometer was inserted into the left ventricle. Absolute volume calibration was accomplished by injection of hypertonic saline into the pulmonary artery. Left ventricular pressures and volumes were simultaneously and continuously measured during transient inferior vena caval occlusion using a balloon catheter. Left ventricular end-systolic pressure-volume relationships were determined during the initial 8-sec of balloon occlusion, before baroreceptor-mediated cardiac stimulation was initiated. OPC-8490 decreased both the left ventricular systolic pressure and end-systolic volume without changing the heart rate. Dobutamine increased the systolic pressure and heart rate but decreased the end-systolic volume. The reduction in the end-systolic volume with dobutamine, was caused by an increase in the slope of the end-systolic pressure-volume relationship, while with OPC-8490, it resulted from a decrease in the end-systolic pressure without an appreciable change in the slope of the end-systolic pressure-volume relationship.(ABSTRACT TRUNCATED AT 250 WORDS)     

Human right ventricular end-systolic pressure-volume relation defined by maximal elastance

This study was undertaken to determine 1) whether a combined radionuclide-hemodynamic technique could define the right ventricular end-systolic pressure-volume relation (RV ESPVR) in the clinical setting, 2) whether the human RV ESPVR defined by maximal elastance is linear and responsive to inotropic interventions, and 3) whether more easily measured modifications of the ESPVR are reliable substitutes as an index of RV function. Eight patients with normal RV function were studied with simultaneous micromanometer RV pressure measurements and radionuclide ventriculography to construct RV pressure-volume loops. Data were collected at baseline and after at least two alterations in loading conditions with nitroglycerin, phenylephrine, or saline. End systole was defined by maximal elastance (E(t) = P(t)/[V(t) - V0]). Data were also obtained during administration of dobutamine in four patients and after atrial pacing tachycardia in one patient. The RV ESPVR defined by maximal elastance was highly linear (r = 0.988-0.999) throughout the range of pressures and volumes tested. Furthermore, the linear correlations were significantly higher (p less than 0.005), and the linear regression standard error of the estimate (SEE) was significantly lower (p less than 0.005) for the RV ESPVR defined by maximal elastance compared with modifications of the ESPVR with the ratio of pulmonary artery-dicrotic notch pressure or RV peak pressure to end-ejection volume. Dobutamine or atrial pacing tachycardia produced a leftward shift of the entire RV pressure-volume loop, and in each patient (five of five), the point of maximal elastance fell outside the 95% confidence interval defined by the baseline ESPVR. However, because of the larger SEE, the leftward shift with modifications of the ESPVR was not statistically significant in any patient by the pulmonary artery-dicrotic notch pressure: end-ejection volume ratio and was significant in only one of five patients by the RV peak pressure: end-ejection volume ratio (p less than 0.03). Therefore, it appears that the steady-state RV ESPVR defined by maximal elastance in patients with normal RV function is responsive to alterations in inotropic state and is more sensitive to alterations in RV function than the frequently used, more easily measured modifications of the RV ESPVR.