Dichloroacetate improves postischemic function of hypertrophied rat hearts

OBJECTIVES We sought to determine whether improving coupling between glucos e oxidation and glycolysis by stimulating glucose oxidation during reperfus ion enhances postischemic recovery of hypertrophied hearts. BACKGROUND Low rates of glucose oxidation and high glycolytic rates are ass ociated with greater postischemic dysfunction of hypertrophied as compared with nonhypertrophied hearts. METHODS Heart function, glycolysis and glucose oxidation were measured in i solated working control and hypertrophied rat hearts for 30 min before 20 m in of global, no-flow ischemia and during 60 min of reperfusion. Selected c ontrol and hypertrophied hearts received 1.0 mmol/liter dichloroacetate (DC A), an activator of pyruvate dehydrogenase, at the time of reperfusion to s timulate glucose oxidation. RESULTS In the absence of DCA, glycolysis was higher and glucose oxidation and recovery of function were lower in hypertrophied hearts than in control hearts during reperfusion. Dichloroacetate stimulated glucose oxidation du ring reperfusion approximately twofold in both groups, while significantly reducing glycolysis in hypertrophied hearts. It also improved function of b oth hypertrophied and control hearts. In the presence of DCA, recovery of f unction of hypertrophied hearts was comparable to or better than that of un treated control hearts. CONCLUSIONS Dichloroacetate, given at the time of reperfusion, normalizes p ostischemic function of hypertrophied rat hearts and improves coupling betw een glucose oxidation and glycolysis by increasing glucose oxidation and de creasing glycolysis. These findings support the hypothesis that low glucose oxidation rates and high glycolytic rates contribute to the exaggerated po stischemic dysfunction of hypertrophied hearts. (J Am Coll Cardiol 2000;36: 1378-85) (C) 2000 by the American College of Cardiology.