Energy metabolism in reperfused heart muscle: Metabolic correlates to return of function

An important question in energy metabolism of the reperfused, previously ischemic myocardium is whether the return of a normal tissue adenosine triphosphate (ATP) content is a prerequisite for normal rates of oxygen consumption (that is, ATP turnover) and cardiac function. To study this problem, isolated working rat hearts were perfused with bicarbonate saline solution containing glucose (10 mM) at near physiologic work load. After 20 minutes, hearts were made totally ischemic by clamping the aortic and atrial lines for 5, 10 or 20 minutes and then were reperfused for another 10 minutes. Heart rate, aortic pressure, cardiac output and myocardial oxygen consumption were measured continuously. Adenine nucleotides, phosphocreatine, glycogen and the products of glycolysis were determined in freezeclamped tissue extracts.Functional recovery was assessed by return of aortic pressure and oxygen consumption to preischemic values. Time required for return of function after reperfusion was 90 seconds after 5 minutes and 124 seconds after 10 minutes of ischemia. No recovery was observed after 20 minutes of ischemia. Tissue ATP content decreased significantly at the end of 5 (- 38%) and 10 (- 56%) minutes of ischemia and did not increase significantly at return of aortic pressure and oxygen consumption to preischemic values. Glycogen stores decreased by more than 50% at the end of 10 minutes of ischemia and did not normalize on recovery. In contrast to ATP or glycogen, the phosphocreatine content decreased to even lower levels at the end of ischemia, but returned to levels higher than the control level after recovery from 5 to 10 minutes of ischemia in association with return of function. These results indicate that transfer of energy-rich phosphate from ATP to creatine during and immediately after reversible ischemia was probably unimpaired. With 5 and 10 minutes of ischemia, lactate and alanine increased significantly and both metabolites were normal on reperfusion. Irreversible impairment of function ensued after 20 minutes of total ischemia in association with an 80% decrease in ATP content and no resynthesis of phosphocreatine or oxidation of lactate.The results demonstrate that 1) rapid resynthesis of phosphocreatine and oxidation of lactate characterizes reversibly damaged ischemic tissue, 2) there is no direct relation between tissue content of ATP and cardiac function, and 3) restoration of oxidative metabolism determines functional recovery of the reperfused ischemic myocardium despite the presence of low ATP levels