Accelerated glycolysis and greater postischemic dysfunction in hypertrophied rat hearts are independent of coronary flow

BACKGROUND: After ischemia, glycolysis and dysfunction are greater, while c oupling of glucose oxidation to glycolysis is lower in hypertrophied hearts than in nonhypertrophied hearts. OBJECTIVE: To test the hypothesis that accelerated glycolysis, reduced coup ling of glucose oxidation to glycolysis and increased postischemic dysfunct ion in hypertrophied hearts compared with nonhypertrophied hearts occur in the absence of differences in coronary flow. MATERIALS AND METHODS: Function, glycolysis and glucose oxidation were meas ured in isolated working control and hypertrophied rat hearts studied for 3 0 min before, and for 40 min after no flow global ischemia for 20 rain unde r conditions in which coronary flow was comparable between the, two groups. The hearts were perfused with 1.2 mmol/L palmitate, 5.5 mmol/L [5-H-3/U-C- 14]-glucose, 0.5 mmol/L lactate, 100 mU/L insulin at a preload of 11.5 mmHg , and an afterload of 60 mmHg in control hearts or 80 mmHg in hypertrophied hearts. RESULTS: Despite comparable rates of coronary flow, functional recovery was lower in hypertrophied hearts than in control hearts. The rates of glycoly sis were accelerated in hypertrophied hearts, while glucose oxidation did n ot significantly differ between the two groups. As a result, the coupling o f glucose oxidation to glycolysis was lower in hypertrophied hearts than in control hearts. CONCLUSIONS. Increased postischemic dysfunction, accelerated glycolysis and reduced coupling of glucose oxidation to glycolysis, in hypertrophied hear ts compared with control hearts cannot be accounted for by differences in c oronary flow. These data provide support for the concept that alterations i n glucose metabolism contribute to the exaggerated postischemic dysfunction of hypertrophied hearts.