EFFECTS OF MODERATE REPETITIVE ISCHEMIA ON MYOCARDIAL SUBSTRATE UTILIZATION

The purpose of this report was to directly measure the influence of an tecedent ischemia or repetitive ischemia on subsequent rates of interm ediary metabolism, specifically exogenous glucose utilization and fatt y acid oxidation, with the use of myocardial equilibrium labeling with [U-C-14]palmitate and [5-H-3]glucose. Twenty-one intact, working, ext racorporeally perfused pig hearts were prepared and divided into three groups. These groups included 7 control hearts and 14 comparison hear ts, which were exposed to either one cycle (cycle 1, n = 7) or four cy cles (cycle 4, n = 7) of brief (5-10 min), moderate (70% decrease in f low below aerobic values) precursory ischemia to the left anterior des cending (LAD) circulation followed by aerobic reperfusion. All groups then underwent a 40 min sustained LAD ischemia (60% decrease in flow b elow aerobic levels) and 40 min aerobic reperfusion. Treatment with on e cycle of transient ischemia did not significantly modify the pattern of glycolytic flux from control values during sustained ischemia (ove r a ninefold increase in average control and cycle 1 values above aero bic levels). However, repetitive ischemia in cycle 4 hearts demonstrab ly attenuated glycolytic flux during the same interval (-45% from cont rol hearts, P < 0.046). Glucose utilization rapidly returned to near-a erobic values in all three groups during reperfusion but was again app reciably lower (P < 0.004 from control values) in cycle 4 hearts. Fatt y 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 f or 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 r eduction of glycolysis noted during both sustained ischemia and reperf usion. In neither intervention group was there an influence on regiona l oxidative metabolism or fatty acid oxidation.