Effect of positive inotropic agents on the relation between oxygen consumption and systolic pressure volume area in canine left ventricle.

Abstract

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, ...

Cardiac Basal Metabolism.

“…This efficiency value does not change much even if the mechanical work per beat is doubled by the use of a substrate such as pyruvate or by the use of inotropic agents such as ouabain or isoprenaline [129,130]. These results are consistent with the constant contractile efficiency measured by Suga and colleagues [103,123] in the presence of agents that alter cardiac contractility. It can be argued that the net mechanical efficiency of afterloaded papillary muscles is overestimated by the recoil of the stretched parallel elastic elements [131][132][133], but because in vivo and in isolated working hearts the ventricles are stretched in diastole by the returning venous blood, we believe that the isolated papillary muscle model approximates reality and that the net efficiency of the heart is close to 20%.…”

Role of myocardium and endothelium in coronary vascular smooth muscle responses to hypoxia

“…Figure 3 shows that the additional relaxation (difference in relaxation between ϩT and ϪT segments) due to the surrounding myocardial tissue is larger than the relaxation of the vessel alone (ϪT segments). It should be noted that the energy need of the cardiac tissue in our preparation is primarily determined by basal metabolism, whereas in actively contracting tissue, the energy need is also determined by excitation-contraction coupling metabolism and mechanical activity associated with cross-bridge turnover (29). Therefore, the contribution of the cardiac myocytes in the beating heart is expected to be stronger.…”

Mechanoenergetics Characterizing Oxygen Wasting Effect of Caffeine in Canine Left Ventricle.

“…The E max -PVA-VO 2 framework is compatible with the Starling law of the heart [9]. In this framework, the O 2 cost of E max serves as a physiologically sound quantitative measure of the O 2 demand for unit increment in E max [5,[10][11][12][13][14][15][16].We have already shown that calcium, catecholamines, digitalis, and phosphodiesterase inhibitors (DPI 201-106, OPC-8212, EMD-53998, milrinone, sulmazole, etc.) have comparable O 2 cost of E max in the normal canine heart [5,10,11,15].…”

“…In this framework, the O 2 cost of E max serves as a physiologically sound quantitative measure of the O 2 demand for unit increment in E max [5,[10][11][12][13][14][15][16].…”