REDUCING LACTATE ACCUMULATION DOES NOT ATTENUATE LETHAL ISCHEMIC-INJURY IN ISOLATED-PERFUSED RAT HEARTS

The role of lactate accumulation in lethal ischemic myocardial cell in jury was assessed by partially depleting hearts of glycogen before isc hemia by using glucagon. Isolated adult rat hearts were perfused with glucose-free Krebs-Henseleit buffer containing acetate as substrate. A fter stabilization, treated hearts were perfused briefly (3 min) with buffer containing 2 mu g/ml glucagon to reduce tissue glycogen stores, followed by 10 min of perfusion with control buffer, and 60 or 90 min of global ischemia. Before the onset of ischemia, glucagon-treated he arts contained 40% less glycogen than untreated hearts, but myocardial function and tissue levels of high-energy phosphates, lactate, and gl ucose 6-phosphate were similar. Lactate production during ischemia in the glucagon-treated hearts was 50% less than in untreated hearts. How ever, there was no decrease in the amount of creatine kinase release d uring reperfusion after either 60 or 90 min of ischemia. Thus although partial glycogen depletion reduced lactate accumulation during ischem ia, this did not decrease the amount of lethal myocardial cell injury.