An assessment of anaerobic metabolism during ischemia and reperfusion in isolated guinea pig heart

Abstract

The effects of total ischemia and subsequent reperfusion on the formation of anaerobic metabolism products and their release into myocardial effluent were studied in isolated guinea pig hearts. During 30-min ischemia myocardial ATP and phosphocreatine decreased to 34 and 15% of the initial levels, respectively; this was accompanied by alanine formation and approximately stoichiometric glutamate loss. The increase in malate in ischemic myocardium corresponded to the anaplerotic flux aspartate----oxaloacetate----malate; the succinate production being commensurable to alpha-ketoglutarate formation in the alanine aminotransferase reaction. The release of lactate, alanine, succinate, creatine and pyruvate trace amounts into the myocardial effluent was observed during an early phase of the reperfusion using 1H-NMR. The rates of metabolite release reduced as follows: lactate much greater than alanine greater than succinate greater than creatine. By the 30th min of the reperfusion the decrease in these metabolites tissue contents was accompanied by the recovery of ATP and phosphocreatine levels up to 65 and 90% of the initial ones, respectively. The data obtained demonstrate that the formation and the release of succinate, alanine and creatine from the heart as well as of lactate may indicate profound disturbances in energy metabolism.