THIMEROSAL ATTENUATES ISCHEMIA-REPERFUSION ARRHYTHMIAS IN RATS - NO MODIFICATION BY ANTIISCHEMIC AGENT TRIMETAZIDINE OR ENDOTHELIN RECEPTORANTAGONIST BOSENTAN

The effects of acyl-coenzyme a: lysolecithin acyltransferase (LAT) inh ibitor thimerosal (20, 30 and 40 mg kg(-1)), anti-ischaemic and free r adical scavenging drug trimetazidine (10 mg kg(-1)) and endothelin ET( A)-ET(B) receptor blocker bosentan [30 mg kg(-1)) were investigated in an anaesthetized rat model of coronary artery ligation (7 min) and re lease (7 min) induced myocardial ischaemia-reperfusion arrhythmias. Ne ither of the drugs produced significant effects on blood pressure exce pt thimerosal which induced a transient fall lasting 5-8 min. The tota l number of ectopic beats during occlusion (controls 141.8+/-73.5, n=1 2) 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; reperfusi on 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 tachycard ia (occlusion 33.9+/-6.1, n=12; reperfusion 94.2+/-18.1, n=10) were al so shortened by thimerosal (occlusion 2.6+/-1.0, n=10, P<0.01; reperfu sion 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, B esides the lack of any effect of trimetazidine, we conclude that endog enous endothelin has no pathophysiological significance in this experi mental model while LAT inhibition does. (C) 1996 The Italian Pharmacol ogical Society