Effect of glucose and of fatty acid on rhythm, enzyme release and oxygen uptake in isolated perfused working rat heart with coronary artery ligation

Abstract

The effects of exogenous substrates on post-occlusion arrhythmias remain controversial because of the difficulty in controlling circulating substrate concentrations in vivo. Isolated working rat hearts, with or without coronary ligation, were perfused in a non-recirculation system with glucose or palmitate as fatty acid. The medium K + was 3.0 m m. Ectopic activity and tachyarrhythmias, chiefly ventricular tachycardia or fibrillation, were quantified as ventricular premature systoles/min or as the duration of ventricular tachycardia or fibrillation (s/min). Hearts were perfused with glucose (5.5 m m) alone, with glucose plus “low” palmitate (0.5 m m bound to albumin 0.25 m m), with glucose plus “high” palmitate (1.5 m m, albumin 0.25 m m) or with “high” palmitate without glucose. Effects on arrhythmias were compared with those on release of lactate dehydrogenase, cardiac output, oxygen uptake, efficiency of work, and the cardiac content of noradrenaline. The striking feature was that hearts perfused with high palmitate without glucose had a severity of ventricular arrhythmias and of depletion of cardiac noradrenaline no greater than hearts perfused with glucose alone. Although glucose-perfused coronary ligated hearts had lower rates of release of enzyme and a more favourable index of efficiency than hearts perfused with palmitate alone in high concentration, the incidence of arrhythmias in these two situations was approximately equal. In this model, palmitate in high concentration is not a potent arrhythmogenic stimulus but markedly increases enzyme release and decreases efficiency of work.