Effects of trimetazidine on metabolic and functional recovery of postischemic rat hearts

The objective of this study was to test the hypothesis that the beneficial effect of trimetazidine during reflow of ischemic hearts is mediated by ene rgy sparing and ATP pool preservation during ischemia. Isolated rat hearts (controls and rats treated with 10(-6) M trimetazidine, n = 17 per group) u ndenwent the following protocol: baseline perfusion at normal coronary flow (20 minutes), low-flow ischemia at 10% flow (60 minutes), and reflow (20 m inutes). me measured contractile function, O-2 uptake, lactate release, ven ous pH and PCO2, and the tissue content of high-energy phosphates and their metabolites. During baseline, trimetazidine induced higher venous pH and l ower PCO2 without influencing performance and metabolism. During low-flow i schemia, trimetazidine reduced myocardial performance (P = 0.04) and ATP tu rnover (P = 0.02). During reflow, trimetazidine improved performance (91 +/ - 6% versus. 55 +/- 6% of baseline), prevented the development of diastolic contracture and coronary resistance, and reduced myocardial depletion of a denine nucleotides and purines. ATP turnover during low-flow ischemia was i nversely related to recovery of the rate-pressure product (P = 0.002), end- diastolic pressure (P = 0.007), and perfusion pressure (P = 0.05). We concl ude that trimetazidine-induced protection of ischemic-reperfused hearts is also mediated by energy sparing during ischemia, which presumably preserves the ATP pool during reflow.