Role of ATP in the maintenance of action potential configuration of the isolated working rat heart.

Abstract

The relation between action potential configuration and myocardial adenosine triphosphate (ATP) concentration was analysed in isolated low and high work rat heart preparations. Glucose used as sole substrate could not provide total energy production when the isolated hearts performed high work. This may explain the decrease in action potential duration and plateau amplitude (phases 2 and 3) that occurred concomitantly with a low total myocardial ATP concentration. When atrial perfusion was changed to the retrograde mode, however, the action potential configuration was restored without an increase in the global myocardial ATP concentration. Pyruvate used as substrate instead of glucose enhanced ATP production by mitochondrial oxidation and partly restored the action potential modifications (principally phase 2). Adenosine added to glucose in the perfusate or infused in situ (before heart isolation and perfusion) enhanced ATP production by the adenine nucleotide salvage pathway and provided a protective effect for phase 2 and 3 action potential variables. The results using glucose as perfusate showed that there was no correlation between global ATP concentration and myocardial electrical activity. An analysis of the other results suggests that the primary problem in the working heart preparation is that the myocardium is in a state of relative hypoxia or ischaemia and that adenosine merely acts as a coronary vasodilator to improve myocardial oxygen delivery.