title: Changes in intracellular sodium and pH during ischaemia-reperfusion are attenuated by trimetazidine. Comparison between low- and zero-flow ischaemia.
abstract: 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.
authors.affiliation: Laboratoire de Physiologie Cellulaire, Université Paris XI, Orsay, France.
authors.forename: H
authors.initials: H
authors.lastname: El Banani
authors.forename: M
authors.initials: M
authors.lastname: Bernard
authors.forename: D
authors.initials: D
authors.lastname: Baetz
authors.forename: E
authors.initials: E
authors.lastname: Cabanes
authors.forename: P
authors.initials: P
authors.lastname: Cozzone
authors.forename: A
authors.initials: A
authors.lastname: Lucien
authors.forename: D
authors.initials: D
authors.lastname: Feuvray
mesh_terms: 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*
chemical_list: D005227:Fatty Acids; D014665:Vasodilator Agents; D012964:Sodium; D014292:Trimetazidine