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 (TI) or low-flow ischaemia (LFI - coronary flow decreased by an average of 90%) (30 min at 37 degrees 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 (pH(i)).


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.


CONCLUSIONS
Our data provide evidence that specific myocardial metabolic modulation plays a significant role in reducing ionic imbalance during ischaemia and reperfusion.
El Banani
H
H
Laboratoire de Physiologie Cellulaire, Université Paris XI, Orsay, France.
Bernard
M
M
Baetz
D
D
Cabanes
E
E
Cozzone
P
P
Lucien
A
A
Feuvray
D
D
D000704:Analysis of Variance; D000818:Animals; D003326:Coronary Circulation; D005227:Fatty Acids / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007424:Intracellular Fluid / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D014292:Trimetazidine / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000627:therapeutic use*
D005227:Fatty Acids; D014665:Vasodilator Agents; D012964:Sodium; D014292:Trimetazidine