© 2000 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Changes in intracellular sodium and pH during ischaemia–reperfusion are attenuated by trimetazidine
Comparison between low- and zero-flow ischaemia
aLaboratoire de Physiologie Cellulaire, Université Paris XI, Orsay, France
bC.R.M.B., Faculté de Médecine Timone, Marseille, France
cI.R.I.S., Courbevoie, France
* Corresponding author. Physiologie Cellulaire, Université Paris Xi, Bât 443, 91405 Orsay Cedex, France. Tel.: +33-1-6915-7898; fax: +33-1-6915-6841 daniellefeuvray{at}ibaic.u-psud.fr
Objective: The aim of this study was to investigate whether trimetazidine (TMZ; 10–6M), 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 (TI) or low-flow ischaemia (LFI — coronary flow decreased by an average of 90%) (30 min at 37°C) and then reperfused. 23Na nuclear magnetic resonance (NMR) spectroscopy was used to monitor intracellular Na+ (Na+i) and 31P NMR spectroscopy was used to monitor intracellular pH (pHi). 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.
KEYWORDS Acidosis; Intra/extracellular ions; Ischemia; NMR; Reperfusion; Ventricular function
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