Changes in intracellular sodium and pH during ischaemia-reperfusion are attenuated by trimetazidine - Comparison between low- and zero-flow ischaemia

Objective: The aim of this study was to investigate whether trimetazidine (TMZ; 10(-6)M), which has been shown to inhibit fatty acid oxidation, reduces the ionic imbalance induced by ischaemia and reperfusion, especially through an attenuation in intracellular changes in H+ and Na+. Methods: Isovolumic rat hearts receiving 5.5 mM glucose and 1.2 mM palmitate as metabolic substrates were exposed to zero-flow ischaemia (TT) or low-flow ischaemia (LFI - coronary flow decreased by an average of 90%) (30 min at 37 degrees C) and then reperfused. Na-23 nuclear magnetic resonance (NMR) spectroscopy was used to monitor intracellular Na+ (Na-i(+)) and P-31 NMR spectroscopy was used to monitor intracellular pH (pH,). Results: During LFI the major effect of TMZ was a significant reduction in intracellular acidosis, whereas during TI the main effect of TMZ was a significant reduction in Na-i(+) gain. In addition, the further gain in Na-i(+) that occurred during the first minutes of reperfusion following TI, and to a far lesser extent following LFI, was suppressed in TMZ-treated hearts and also suppressed when hearts were perfused without Fatty acid. In both LFI and TI, TMZ-induced attenuation of ionic imbalance was associated with a significantly improved recovery of ventricular function on reperfusion, as assessed by a lower increase in diastolic pressure and an increased recovery of developed pressure. Conclusion: Our data provide evidence that specific myocardial metabolic modulation plays a significant role in reducing ionic imbalance during ischaemia and reperfusion. (C) 2000 Elsevier Science B.V. All rights reserved.