CARDIAC EFFICIENCY IS IMPROVED AFTER ISCHEMIA BY ALTERING BOTH THE SOURCE AND FATE OF PROTONS

Cardiac efficiency is decreased in hearts after severe ischemia. We de termined whether reducing the production of H+ from glucose metabolism or inhibiting the clearance of H- via Na--H+ exchange could increase cardiac efficiency during reperfusion. This was achieved using dichlor oacetate (DCA) to stimulate glucose oxidation and 5-(N,N-dimethyl)-ami loride (DMA) to inhibit Na+-H+ exchange. respectively. Isolated workin g rat hearts were subjected to 30 minutes of global ischemia and 60 mi nutes of reperfusion. Glycolysis and oxidation rates of glucose, lacta te, and palmitate were measured. Recovery of cardiac work, O-2 consump tion (MVO(2)), and rates of acetyl-coenzyme A and ATP production durin g reperfusion were determined. After ischemia, cardiac work recovered to 35 +/- 5% of preischemic values in control hearts (n = 23), althoug h MVO(2). tricarboxylic acid (TCA) cycle activity, and ATP production from glycolysis and oxidative metabolism rapidly recovered to preische mic levels. This decrease in cardiac efficiency was accompanied by a s ubstantial production of H- from glucose metabolism. DCA caused a 2.2- fold increase in glucose oxidation, a 46 +/- 17% decrease in H- produc tion, a 10-fold increase in cardiac efficiency, and a 2.0-fold increas e in cardiac work during reperfusion (n = 17). Inhibition of Na+-H+ ex change with DMA did not alter TCA cycle activity and ATP production ra tes but did result in a 1.8-fold increase in cardiac efficiency and a 1.7-fold increase in cardiac work (n = 12). These data show that cardi ac efficiency and the contractile function after ischemia can be impro ved by either reducing the rate of H+ production from glucose metaboli sm during reperfusion or inhibiting the clearance of H+ via Na+-H+ exc hange. Our data suggest that an increased requirement for ATP to resto re ischemia-reperfusion-induced alterations in ion homeostasis contrib utes to the decrease in cardiac efficiency and contractile function af ter ischemia.