The role of ATP depletion and accumulated metabolic products during myocardial ischemia

Abstract

Over the past few years we have directed a considerable amount of effort toward identification of the sequence of biochemical changes which result in a transition of ischemic myocardium from reversibly damaged to irreversibly damaged tissue. For most of the studies that I will describe we have used the isolated perfused rat heart which is exposed to global ischemia. The general protocol that we have followed consists of perfusion of the heart under normal aerobic conditions for a period of 10 min (Fig. 1, top panel). Ischemia, either at zero coronary flow or any reduced flow desired is then instituted for various times and the heart is reperfused for 30 min under normal aerobic conditions. Recovery of ventricular function and restorations of tissue metabolites are followed. If the tissue is reperfused early in ischemia the ventricle will recover metabolically and functionally without much difficulty. It is not surprising, however, that the longer the ischemic period is prolonged, the worse the recovery becomes with reperfusion. The top panel in Fig. 1 shows the change in metabolites and depression of ventricular function after 30 min of zero coronary flow.