Thimerosal attenuates ischaemia-reperfusion arrhythmias in rats: no modification by anti-ischaemic agent trimetazidine or endothelin receptor antagonist bosentan.
The effects of acyl-coenzyme a: lysolecithin acyltransferase (LAT) inhibitor thimerosal (20, 30 and 40 mg kg-1), anti-ischaemic and free radical scavenging drug trimetazidine (10 mg kg-1) and endothelin ETA-ETB receptor blocker bosentan [30 mg kg-1) were investigated in an anaesthetized rat model of coronary artery ligation (7 min) and release (7 min) induced myocardial ischaemia-reperfusion arrhythmias. Neither of the drugs produced significant effects on blood pressure except thimerosal which induced a transient fall lasting 5-8 min. The total number of ectopic beats during occlusion (controls 141.8 +/- 73.5, n = 12) and reperfusion (controls 1151.1 +/- 199.1, n = 10) was not modified by either trimetazidine (occlusion 452.5 +/- 128.6, n = 10; reperfusion 1002.0 +/- 198.4, n = 6) or bosentan (occlusion 431.2 +/- 112.8, n = 10; reperfusion 1530.7 +/- 296.8, n = 9) while thimerosal attenuated them (occlusion 50.2 +/- 14.9, n = 10, P < 0.01 vs controls; reperfusion 345.1 +/- 83.8, n = 8, P < 0.01 vs controls). The durations (in seconds) of ventricular tachycardia (occlusion 33.9 +/- 6.1, n = 12; reperfusion 94.2 +/- 18.1, n = 10) were also shortened by thimerosal (occlusion 2.6 +/- 1.0, n = 10, P < 0.01; reperfusion 28.5 +/- 7.8, n = 8, P < 0.01) while trimetazidine or bosentan did not significantly modify them. The incidences of ventricular fibrillation or mortality were not significantly modified by either of the drugs. Besides the lack of any effect of trimetazidine, we conclude that endogenous endothelin has no pathophysiological significance in this experimental model while LAT inhibition does.
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Department of Pharmacology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
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D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D001794:Blood Pressure / Q000187:drug effects; D000077300:Bosentan; D065128:Endothelin Receptor Antagonists; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology*; D017180:Tachycardia, Ventricular / Q000188:drug therapy; D013849:Thimerosal / Q000494:pharmacology*; D014292:Trimetazidine / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D065128:Endothelin Receptor Antagonists; D004791:Enzyme Inhibitors; D013449:Sulfonamides; D014665:Vasodilator Agents; D013849:Thimerosal; D014292:Trimetazidine; D000077300:Bosentan