EFFECTS OF MODERATE REPETITIVE ISCHEMIA ON MYOCARDIAL SUBSTRATE UTILIZATION

The purpose of this report was to directly measure the influence of antecedent ischemia or repetitive ischemia on subsequent rates of intermediary metabolism, specifically exogenous glucose utilization and fatty acid oxidation, with the use of myocardial equilibrium labeling with [U-C-14]palmitate and [5-H-3]glucose. Twenty-one intact, working, extracorporeally perfused pig hearts were prepared and divided into three groups. These groups included 7 control hearts and 14 comparison hearts, which were exposed to either one cycle (cycle 1, n = 7) or four cycles (cycle 4, n = 7) of brief (5-10 min), moderate (70% decrease in flow below aerobic values) precursory ischemia to the left anterior descending (LAD) circulation followed by aerobic reperfusion. All groups then underwent a 40 min sustained LAD ischemia (60% decrease in flow below aerobic levels) and 40 min aerobic reperfusion. Treatment with one cycle of transient ischemia did not significantly modify the pattern of glycolytic flux from control values during sustained ischemia (over a ninefold increase in average control and cycle 1 values above aerobic levels). However, repetitive ischemia in cycle 4 hearts demonstrably attenuated glycolytic flux during the same interval (-45% from control hearts, P < 0.046). Glucose utilization rapidly returned to near-aerobic values in all three groups during reperfusion but was again appreciably lower (P < 0.004 from control values) in cycle 4 hearts. Fatty acid oxidation averaged 12.3 +/- 1.2 mu mol . h(-1). g dry wt(-1) in all three groups during sustained ischemia and 21.3 +/- 2.0 mu mol . h(-1). g dry wt(-1) during reperfusion (not significant among groups for either perfusion interval). In conclusion, the metabolic effects of precedent treatment with transient, moderate ischemia were dependent on cycle number, and in the cycle 4 group it resulted in a selective reduction of glycolysis noted during both sustained ischemia and reperfusion. In neither intervention group was there an influence on regional oxidative metabolism or fatty acid oxidation.