As a means of assessing ventricular performance, we analyzed the time-varying ratio of instantaneous pressure, P(t), to instantaneous volume, V(t), in the canine left ventricle. Intraventricular volume was measured by plethysmography, while the right heart was totally bypassed. The cardiac nerves were sectioned, and an epinephrine infusion was used to alter the contractile state. The instantaneous pressure-volume ratio was defined aswhere V d is an experimentally determined correction factor. We found that (1) all the E(t) curves thus defined were similar in their basic shape and attained their peak near the end of the ejection phase regardless of the mechanical load, the contractile state, or the heart rate, (2) under a constant heart rate and contractile state extensive changes in preload, afterload, or both did not alter the peak value of E ( t ) , Emax, or the time to Emax from the onset of systole, Tmax, and (3) these parameters of E(t) markedly changed with epinephrine infusion or increases in heart rate. At an epinephrine infusion rate of 2 fig/kg min" 1 , Emax increased to 12.2 ± 4.5 (SD) mm Hg/ml (N = 9) from its control value of 6.6 ± 1.2 mm Hg/ml before the infusion. Simultaneously, Tmax shortened from 191 ± 29 msec to 157 ± 26 msec. Increases in the paced heart rate proportionally shortened Tmax (45% per 100-beats/min change in heart rate) without any effect on Emax. We concluded that E ( t ) , represented by Emax and Tmax, explicitly reflects the ventricular contractility.

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We have previously shown in the normally ejecting canine left ventricle that E ( t ), the time-varying ratio of instantaneous pressure, P ( t ), to instantaneous volume, V ( t ), is little affected by end-diastolic volume or aortic pressure. The present study on an excised, supported canine heart preparation indicates that the thesis on E ( t ) is also valid for either totally isovolumic or auxobaric beats. Intraventricular volume was measured more accurately than it was in the previous study by a new volumetric system. Regression analysis of the data showed that the instantaneous pressure-volume relationship could be approximated by the equation P ( t ) = E ( t ).[ V ( t ) - V d ], where V d is an empirical constant, over a wide range of intraventricular volume. Similar E ( t ) curves were obtained from both isovolumic and auxobaric beats for a given contractile state. When the contractile state of the preparation was enhanced by a constant-rate infusion (0.2 µg/min) of norepinephrine or isoproterenol into the coronary artery, the peak magnitude of E ( t ) increased 63% from 3.6 mm Hg/ml and the time to peak E ( t ) shortened 10% from 175 msec. We conclude that the present investigation substantiates our earlier study which established a link between E ( t ) and the contractile state of the heart.

Assessment of left ventricular systolic and diastolic pump properties is fundamental to advancing the understanding of cardiovascular pathophysiology and therapeutics, especially for heart failure. The use of end-systolic and end-diastolic pressure-volume relationships derived from measurements of instantaneous left ventricular pressure-volume loops emerged in the 1970s as a comprehensive approach for this purpose. As invasive and noninvasive techniques for measuring ventricular volume improved over the past decades, these relations have become commonly used by basic, translational, and clinical researchers. This review summarizes 1) the basic concepts underlying pressure-volume analysis of ventricular and myocardial systolic and diastolic properties, 2) deviations from ideal conditions typically encountered in real-life applications, 3) how these relationships are appropriately analyzed, including statistical analyses, and 4) the most common problems encountered by investigators and the appropriate remedies. The goal is to provide practical information and simple guidelines for accurate application and interpretation of pressure-volume data as they pertain to characterization of ventricular and myocardial properties in health and disease.

Mechanical energy (ENG) required by a time-varying elastance model of the ventricle was compared with oxygen consumption per beat (VO2) of the canine left ventricle contracting under a variety of loading conditions. ENG needed for this model to increase its elastance during systole is shown to be equal to the sum of the potential energy built in the elastance during systole plus the external mechanical stroke work. This ENG is equivalent to the area (PVA) bounded by the end-systolic and end-diastolic P-V curves and the systolic limb of the P-V loop trajectory in the P-V plane. There was a high correlation (r = 0.89) between VO2s documented in the literature and PVAs assessed by the author from the accompanying P-V data from both isovolumic and ejecting contractions in 11 hearts. A linear regression analysis yielded an empirical equation: VO2 (ml O2/beat) = a . PVA (mmHg . ml/beat) + b, where a = 1.37 X 10(-5) and b = 0.027, which can be used to predict VO2 from PVA. A preliminary experimental study in my laboratory confirmed the validity of this empirical equation.

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SUMMARY. We analyzed the effect of positive inotropic agents on the relation between left ventricular oxygen consumption and the systolic pressure-volume area. Pressure-volume area is a measure of total mechanical energy for ventricular contraction, and is a specific area in the ventricular pressure-volume diagram circumscribed by the end-systolic and end-diastolic pressurevolume relation curves and the systolic segment of the pressure-volume trajectory. Either epinephrine (1 Mg/kg per min, iv) or calcium ion (0.03 mEq/kg per min, iv) was administered to canine excised cross-circulated hearts. These agents increased an index of ventricular contractility, Emax, or the slope of the end-systolic pressure-volume line, by 70%. The regression lines of ventricular oxygen consumption on pressure-volume area in control and in enhanced contractile states were of the same formula: ventricular oxygen consumption (ml 02/beat per 100 g) equals A times pressure-volume area (mm Hg ml/beat per 100 g) plus a constant B. Coefficient A remained unchanged at 1.8 X 10~5 ml oxygen/(mm Hg ml), but constant B increased from 0.03 ml oxygen/beat per 100 g by more than 50% with either agent. The reciprocal of A reflects the energy conversion efficiency for the total mechanical energy, and this efficiency remained near 36%. The increase in B was equal to the directly measured increment in ventricular oxygen consumption for mechanically unloaded contraction. The basal metabolism remained unchanged. We conclude that the augmented oxygen consumption under the acutely enhanced contractile state with either epinephrine or calcium was caused primarily by an increased energy utilization associated with the excitation-contraction coupling. (Circ Res 53: 306-318, 1983) ENHANCEMENT of cardiac contractile state with an acutely administered positive inotropic agent is generally associated with an increase in cardiac energy utilization and oxygen consumption (Braunwald, 1969;Gibbs and Chapman, 1979). The increment in energy utilization for a given measure of mechanical contraction has been called oxygenwasting effect of the positive inotropic agent (Chandler et al., 1968;Rooke and Feigl, 1982). Although quantitative relations between the augmented energetics and the enhanced contraction have been analyzed (Sonnenblick et al., 1965;Gibbs, 1978), the mechanism of the oxygen-wasting effect has not been fully elucidated, and has been ascribed either to the enhancement of contractile state in terms of the increase in the shortening velocity (V^) of myocardium (Sonnenblick et al., 1965, Braunwald, 1969 or to the increased generation of force-independent heat associated with augmented calcium release and retrieval in the enhanced contractile state (Gibbs and Gibson, 1972;Gibbs, 1978). In addition, the effect of the positive inotropic agent on energy conversion efficiency for mechanical contraction has not been analyzed explicitly in relation to the oxygen-wasting effect. One major reason for this situation seems to be that the mechanical parameters (force, ...

The aim of the present study was to examine the mechanisms of Ca2+ overload-induced contractile dysfunction in rat hearts independent of ischemia and acidosis. Experiments were performed on 30 excised cross-circulated rat heart preparations. After hearts were exposed to high Ca2+, there was a contractile failure associated with a parallel downward shift of the linear relation between myocardial O(2) consumption per beat and systolic pressure-volume area (index of a total mechanical energy per beat) in left ventricles from all seven hearts that underwent the protocol. This result suggested a decrease in O(2) consumption for total Ca2+ handling in excitation-contraction coupling. In the hearts that underwent the high Ca2+ protocol and had contractile failure, we found marked proteolysis of a cytoskeleton protein, alpha-fodrin, whereas other proteins were unaffected. A calpain inhibitor suppressed the contractile failure by high Ca2+, the decrease in O(2) consumption for total Ca2+ handling, and membrane alpha-fodrin degradation. We conclude that the exposure to high Ca2+ may induce contractile dysfunction possibly by suppressing total Ca2+ handling in excitation-contraction coupling and degradation of membrane alpha-fodrin via activation of calpain.