H. El Banani et al., Changes in intracellular sodium and pH during ischaemia-reperfusion are attenuated by trimetazidine - Comparison between low- and zero-flow ischaemia, CARDIO RES, 47(4), 2000, pp. 688-696
Citations number
47
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Objective: The aim of this study was to investigate whether trimetazidine (
TMZ; 10(-6)M), which has been shown to inhibit fatty acid oxidation, reduce
s the ionic imbalance induced by ischaemia and reperfusion, especially thro
ugh an attenuation in intracellular changes in H+ and Na+. Methods: Isovolu
mic rat hearts receiving 5.5 mM glucose and 1.2 mM palmitate as metabolic s
ubstrates were exposed to zero-flow ischaemia (TT) or low-flow ischaemia (L
FI - coronary flow decreased by an average of 90%) (30 min at 37 degrees C)
and then reperfused. Na-23 nuclear magnetic resonance (NMR) spectroscopy w
as used to monitor intracellular Na+ (Na-i(+)) and P-31 NMR spectroscopy wa
s used to monitor intracellular pH (pH,). Results: During LFI the major eff
ect of TMZ was a significant reduction in intracellular acidosis, whereas d
uring 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 m
inutes of reperfusion following TI, and to a far lesser extent following LF
I, was suppressed in TMZ-treated hearts and also suppressed when hearts wer
e 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 di
astolic pressure and an increased recovery of developed pressure. Conclusio
n: Our data provide evidence that specific myocardial metabolic modulation
plays a significant role in reducing ionic imbalance during ischaemia and r
eperfusion. (C) 2000 Elsevier Science B.V. All rights reserved.