Simultaneous assessment of the effects of trimetazidine on the myocardium and coronary vasculature of the dog

The effects of trimetazidine on the electrical and mechanical activities of the myocardium were investigated in comparison with the effect on the coronary blood flow in blood-perfused preparations excised from dog hearts. In the sinoatrial (SA) node preparation, trimetazidine injected into the sinus node artery increased blood flow and depressed SA node automaticity. In the atrioventricular (AV) node preparation, trimetazidine injected into the AV node artery or the anterior septal artery increased blood flow and equally prolonged AV conduction time. In the capillary muscle preparation, trimetazidine injected into the anterior septal artery increased blood flow and depressed force of contraction. These cardiodepressant actions occurred in the same range of doses of trimetazidine that exerted the vasodilator action. This indicates that trimetazidine has no selective activity on the coronary vasculature alone. Moreover, the vasodilator effect was more short-lived than the cardiodepressant action. Trimetazidine injected into the anterior septal artery affected ventricular bipolar electrograms. This, taken together with the prolongation of AV conduction time obtained with the same route of administration, suggests that the cardiodepressant action of trimetazidine is ascribed to the local anesthetic or the membrane stabilizing action rather than to the calcium-antagonistic action.