Recent studies have shown that myocardial oxygen consumption does not proportionally decrease with the deterioration of contractile function in stunned myocardium. To investigate this disproportion, we studied the end-systolic pressure-volume relation and the relation between oxygen consumption per beat (VO2) and systolic pressure-volume area (PVA, a measure of total mechanical energy) in stunned hearts. In the VO2-PVA relation, VO2 can be divided into PVA-dependent and PVA-independent fractions. In excised cross-circulated dog left ventricles, a 15-minute normothermic global ischemia followed by 60-120 minutes of reperfusion significantly decreased the ventricular contractility index (Emax) by approximately 40%, but the PVA-independent VO2 did not significantly decrease. Oxygen cost of PVA, defined as the slope of the VO2-PVA relation, was slightly decreased in stunned hearts. Restoration of the depressed Emax to the preischemic control level by calcium infusion increased the PVA-independent VO2 to 137 +/- 27% of control level (p less than 0.01). Oxygen cost of contractility, defined as the slope of the relation between PVA-independent VO2 and Emax, increased from 0.0011 +/- 0.0003 to 0.0023 +/- 0.0005 ml O2.ml.mm Hg-1.beat-1 per 100 g myocardium in control and stunned hearts, respectively (p less than 0.01). From these new finding, we conclude that the unchanged VO2, despite the depressed contractility in stunned myocardium, is mainly due to the increased oxygen cost of contractility.

We studied the effects of ventricular end-systolic elastance (Ees) and effective arterial elastance (Ea) on the efficiency of energy transfer from pressure-volume area (PVA) to external mechanical work (EW) in the left ventricle of anesthetized closed-chest dogs. PVA represents the total mechanical energy generated by ventricular contraction, which is an intermediate form of energy between oxygen consumption, the total energy input, and EW, the effective energy output. PVA and EW were determined from ventricular pressure and volume, which were continuously measured with a volumetric conductance catheter. Measurements of Ees were obtained by transiently increasing afterload by an inflation of a Fogarty catheter in the thoracic descending aorta. Ea was determined as the ratio of end-systolic pressure to stroke volume. The EW/PVA efficiency of a steady-state contraction increased from 55% to 64%, with a 58% increase in Ees after dobutamine. Ees, which was smaller than Ea before dobutamine, became nearly equal to Ea after dobutamine, maximizing EW for a given end-diastolic volume. EW/PVA efficiency decreased with an abrupt increase in afterload before and after dobutamine. The sensitivity of the decrease in the EW/PVA efficiency to an increase in end-systolic pressure was significantly less after than before dobutamine. We could account for all these changes in EW/PVA efficiency by the relative changes in Ees and Ea in the pressure-volume diagram.

We studied the effects of cardiac cooling by 7 +/- 2 degrees C (SD) from 36 degrees C on both contractility index (Emax) and the relation between O2 consumption per beat (VO2) and systolic pressure-volume area (PVA) of the left ventricle in the excised cross-circulated dog heart preparation. PVA represents the total mechanical energy generated by a contraction. The VO2-PVA relation divides measured VO2 into unloaded VO2 and excess VO2. The slope of the VO2-PVA relation represents inversely the efficiency of the contractile machinery to convert chemical energy from the excess VO2 to total mechanical energy. Cooling is known to decrease myosin ATPase activity (Q10 of 2-3), which in turn is expected to increase the chemomechanical efficiency of cross bridges. Therefore, we expected an increase in the efficiency and hence a decreased slope of the VO2-PVA relation with cooling. The cooling increased Emax by 46 +/- 13% and the time to Emax by 45 +/- 27%. Pacing rate was constant or had to be slightly decreased to avoid arrhythmias with cooling. We found that neither the slope of the VO2-PVA relation nor unloaded VO2 significantly (p greater than 0.05) changed with the cooling. This result contradicts the expected increase in the efficiency with cooling. We conclude that cardiac cooling by 7 degrees C from 36 degrees C does not increase the efficiency of the contractile machinery in excised cross-circulated dog left ventricle.

We investigated the contribution of maximal Ca(2+)-activated force to the positive inotropism induced by mild hypothermia. Phosphorus-31 nuclear magnetic resonance spectroscopy revealed that neither energy-related phosphorus compounds in myocardium nor intracellular pH was responsible for the change in contractility. Maximal Ca(2+)-activated pressure (MCAP), the intact-heart correlate of maximal Ca(2+)-activated force, was determined in isolated perfused rabbit hearts by measuring isovolumic left ventricular pressure during tetani at extracellular Ca2+ concentrations greater than or equal to 10 mM. Tetani were elicited by rapid pacing after exposure to ryanodine. MCAP increased by 2.17 +/- 0.28% (mean +/- SE, P less than 0.001, n = 19) for each degree of myocardial cooling between 30 and 38 degrees C. Our results indicate that a primary change in myofilament Ca2+ responsiveness underlies the positive inotropism in hypothermia. The increase in maximal Ca(2+)-activated force may explain the observation of positive inotropism without an upward shift in the relation between oxygen consumption and pressure-volume area, as previously reported for cooled whole hearts.