Assessment of techniques for preventing glycolysis in cardiac muscle

Abstract

Studies of myocardial function during ischaemia or anoxia would be assisted if it were possible to inhibit glycolysis completely and reversibly. Three methods of preventing glycolysis in isolated perfused ferret hearts were studied: (a) the removal of glucose from the perfusate followed by manoeuvres designed to deplete glycogen stores, (b) the use of 2-deoxyglucose, and (c) the use of iodoacetate. The rate of glycolysis before and after applying the three methods was assessed by measuring lactate production during short periods of anoxia. Metabolic changes associated with each method were investigated with phosphorus nuclear magnetic resonance, and other side effects associated with each method were assessed by measuring developed pressure. The results show that removal of glucose followed by glycogen depletion reduced the rate of glycolysis to any chosen extent and that the method was reversible. 2-Deoxyglucose treatment did not lead to complete inhibition of glycolysis, was not reversible, and reduced the concentrations of phosphocreatine and adenosine triphosphate in the heart. Iodoacetate treatment completely blocked glycolysis, but it was not reversible and subsequent periods of anoxia lead to a rapid fall in adenosine triphosphate owing to the accumulation of phosphorylated glycolytic intermediates.