Ionic and metabolic imbalance as potential factors of ischemia reperfusion injury

This study examined the influence of metabolic substrates on the effects of trimetazidine on functional and metabolic aspects of the ischemic reperfused heart. Isovolumic rat hearts were submitted to a 30-minute period of global mild ischemia (coronary flow decreased by an average of 70%) and then reperfused at constant preischemic coronary flow rate. Either glucose (11 mM) or glucose and palmitic acid (0.1 mM) were used as metabolic substrates. Trimetazidine (6 x 10(-7)M) markedly reduced the increase in diastolic pressure that occurred on reperfusion after the ischemic episode, whatever the exogenous substrate used. However, in those hearts that received fatty acid, the postischemic increase in diastolic pressure was abolished. Ischemia-induced increase in acyl carnitine levels-determined as indicators of fatty acid utilization by myocardial cells-was significantly decreased by trimetazidine in those hearts receiving fatty acid. Also, similar effects to those of trimetazidine on the postischemic increase in diastolic pressure and on tissue levels of acyl carnitine were obtained in the presence of dichloroacetate. Moreover, the presence of trimetazidine was associated with a reduction in the intracellular pH decrease during ischemia in those hearts receiving fatty acid. Combined with previous studies, these results suggest that an improved metabolic balance by trimetazidine may well consequently decrease the ionic imbalance after a transient period of ischemia.