IONIC AND METABOLIC IMBALANCE AS POTENTIAL FACTORS OF ISCHEMIA-REPERFUSION INJURY

This study examined the influence of metabolic substrates on the effec ts of trimetazidine on functional and metabolic aspects of the ischemi c reperfused heart. Isovolumic rat hearts were submitted to a 30-minut e period of global mild ischemia (coronary flow decreased by an averag e of 70%) and then reperfused at constant preischemic coronary flow ra re. Either glucose (11 mM) or glucose and palmitic acid (0.1 mM) were used as metabolic substrates. Trimetazidine (6 x 10(-7) M) markedly re duced the increase in diastolic pressure that occurred on reperfusion after the ischemic episode, whatever the exogenous substrate used. How ever, in those hearts that received fatty acid, the postischemic incre ase in diastolic pressure was abolished. Ischemia-induced increase in acyl carnitine levels-determined as indicators of fatty acid utilizati on 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 o n tissue levels of acyl carnitine were obtained in the presence of dic hloroacetate. Moreover, the presence of trimetazidine was associated w ith a reduction in the intracellular pH decrease during ischemia in th ose hearts receiving fatty acid. Combined with previous studies, these results suggest that an improved metabolic balance by trimetazidine m ay well consequently decrease the ionic imbalance after a transient pe riod of ischemia. (C) 1998 by Excerpta Medica, Inc.