High levels of fatty acids delay the recoveryof intracellular pH and cardiac efficiency inpost-ischemic hearts by inhibiting glucose oxidation

Abstract

ObjectivesThis study was designed to determine if the fatty acid-induced increase in H+production from glycolysis uncoupled from glucose oxidation delays the recovery of intracellular pH (pHi) during reperfusion of ischemic hearts. BackgroundHigh rates of fatty acid oxidation inhibit glucose oxidation and impair the recovery of mechanical function and cardiac efficiency during reperfusion of ischemic hearts. MethodspHiwas measured by 31P nuclear magnetic resonance spectroscopy in isolated working rat hearts perfused in the absence (5.5 mmol/l glucose) or presence of 1.2 mmol/l palmitate (glucose+palmitate). Glycolysis and glucose oxidation were measured using [5-3H/U-14C]glucose. ResultsWhen glucose+palmitate hearts were subjected to 20 min of no-flow ischemia, recoveries of mechanical function and cardiac efficiency were significantly impaired compared with glucose hearts. Glucose oxidation rates were significantly lower in glucose+palmitate hearts during reperfusion compared with glucose hearts, whereas glycolysis rates were unchanged. This resulted in an increase in H+production from uncoupled glucose metabolism, and a decreased rate of recovery of pHiin glucose+palmitate hearts during reperfusion compared with glucose-perfused hearts. Dichloroacetate (3 mmol/l) given at reperfusion to glucose+palmitate hearts resulted in a 3.2-fold increase in glucose oxidation, a 35% ± 3% decrease in H+production from glucose metabolism, a 1.7-fold increase in cardiac efficiency and a 2.2-fold increase in the rate of pHirecovery during reperfusion. ConclusionsA high level of fatty acid delays the recovery of pHiduring reperfusion of ischemic hearts because of an increased H+production from glycolysis uncoupled from glucose oxidation. Improving the coupling of glucose metabolism by stimulating glucose oxidation accelerates the recovery of pHiand improves both mechanical function and cardiac efficiency.