Comparison of the Effects of Anoxia and Whole Heart Ischemia on Carbohydrate Utilization in Isolated Working Rat Hearts

Abstract

The rates of utilization of glycogen and exogenous glucose by hearts perfused at low coronary flows and high perfusate oxygen tension (ischemia) and by hearts perfused at high coronary flows and low perfusate oxygen tension (anoxia) were studied in the isolated, working rat heart. Ischemic tissue had a glycolytic rate that was 25% of the anoxic rate and 50% of the control rate. Inhibition of carbohydrate utilization during ischemia was due to a lower flux through the glycolytic pathway and not to a lower rate of glucose transport or substrate availability. Insulin and elevated perfusate glucose increased glucose transport and caused accumulation of free intracellular glucose, but ischemia still inhibited glucose utilization. Insulin failed to maintain tissue levels of high-energy phosphates or to prevent mechanical failure in ischemic hearts. In the absence of insulin, tissue lactate increased tenfold during 20 minutes of ischemia, although it increased only threefold in anoxic tissue. The increased tissue lactate in ischemic hearts corresponded to the inhibition of glycolysis and to the failure of mechanical performance. Insulin caused a further increase in tissue lactate during ischemia. These findings illustrate several important differences between anoxia and ischemia and suggest that insulin may be more harmful than it is beneficial in severely ischemic tissue.