This 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 (pH_i) during reperfusion of ischemic hearts.

High rates of fatty acid oxidation inhibit glucose oxidation and impair the recovery of mechanical function and cardiac efficiency during reperfusion of ischemic hearts.

pH_iwas 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.

When 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 pH_iin 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 pH_irecovery during reperfusion.

A high level of fatty acid delays the recovery of pH_iduring 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 pH_iand improves both mechanical function and cardiac efficiency.