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

BACKGROUND: After ischemia, glycolysis and dysfunction are greater, while coupling of glucose oxidation to glycolysis is lower in hypertrophied hearts than in nonhypertrophied hearts. OBJECTIVE: To test the hypothesis that accelerated glycolysis, reduced coupling of glucose oxidation to glycolysis and increased postischemic dysfunction 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 measured in isolated working control and hypertrophied rat hearts studied for 30 min before, and for 40 min after no flow global ischemia for 20 min under 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 [5-3H/U-14C]-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 glycolysis were accelerated in hypertrophied hearts, while glucose oxidation did not significantly differ between the two groups. As a result, the coupling of 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 hearts compared with control hearts cannot be accounted for by differences in coronary flow. These data provide support for the concept that alterations in glucose metabolism contribute to the exaggerated postischemic dysfunction of hypertrophied hearts.