Influence of isoproterenol on myocardial energetics. Experimental and clinical investigations

The influence of isoproterenol on myocardial performance and energetics was investigated in normal guinea pig myocardium and in patients with normal left ventricular function. The in vitro experiments were performed by simultaneous isometric force and heat measurements using sensitive antimony-bismuth thermopiles. Following the application of isoproterenol (10(-8) M) isometric peak twitch tension and tension-time integral increased significantly by 185% and 142%, respectively. Tension-independent heat which reflects high energy phosphate hydrolysis of excitation-contraction coupling increased by 183%. Tension-dependent heat reflecting the high energy phosphate hydrolysis of the crossbridges increased by 417%. The ratio of tension-dependent heat to tension-time integral increased by 131%. The recovery/initial heat ratio, reflecting the efficiency of the recovery metabolism, and the resting metabolism did not significantly change. In the patients the effect of isoproterenol on myocardial energetics was evaluated in terms of myocardial efficiency. Following isoproterenol administration, left ventricular systolic stress-time integral decreased by 49% due to reductions in end-diastolic pressure, end-diastolic volume and duration of systole. Pressure-volume work remained unchanged. Myocardial oxygen consumption per minute increased in proportion to heart rate. The ratio of myocardial oxygen consumption per beat to left ventricular systolic stress-time integral increased significantly by 95%. External myocardial efficiency was unaltered. Thus, isoproterenol increases the energy turnover of excitation-contraction coupling and increases the energy consumption of the crossbridges disproportionately to developed tension-time integral in the guinea pig heart.