EFFECTS OF TRIMETAZIDINE ON INVIVO CORONARY ARTERIAL PLATELET THROMBOSIS

We used Folts' model of critical coronary artery stenosis with endothe lial damage, which measures platelet-rich thrombus accumulation from c yclic flow reductions (CFRs). This paper reports results applied to tr imetazidine, a member of the piperazine group. Trimetazidine at a dose of 1 mg/kg completely abolished CFRs caused by accumulating thrombus in the circumflex coronary artery in 4 of 8 open-chest anesthetized be agles. More trimetazidine (up to 5 mg/kg) abolished CFRs in two more a nd attenuated them in the remaining two dogs. There were no systemic h emodynamic effects observed. Adrenaline was then infused to stimulate platelet activation. At a rate of 0.4 mug/kg/min, CFRs were restored i n one dog only. Adrenaline given at 1.6 mug/kg/min resulted in restora tion or increase in the slope of CFRs in all animals. A further six no noperated dogs were anesthetized and given trimetazidine 3 mg/kg. Rout ine coagulation studies were not altered. However, aspirin 5 mg/kg sig nificantly increased bleeding time, whereas trimetazidine alone did no t. These findings suggest that trimetazidine is effective in preventin g intracoronary platelet aggregation in this model. Because of its dem onstrated sparing of coagulation factors and its lack of effect on ble eding time, the cause is unlikely to be inhibition of the fibrinogen o r thrombin receptors, or interference with arachidonic acid metabolism .