Inhibitory effect of trimetazidine on thrombin-induced aggregation and calcium entry into human platelets

The antiaggregatory properties of trimetazidine were investigated further by analyzing its effects on cytosolic calcium and proton concentrations, well-known regulators of platelet reactivity. Aggregatory responses of washed platelets were assessed by turbidometry, and cytosolic Ca 2+ concentration ([Ca 2+ ] i ) and pH (pH i ) were determined by their respective fluorescent probes: Fura-2 and BCECF. Preincubation with trimetazidine dose/dependently inhibited platelet aggregation induced by 0.05 U/ml thrombin (p<0.001). At concentrations ≤1 mM, trimetazidine did not affect the resting [Ca 2+ ] i value but slightly alkalinized the cytosol by 0.05±0.03 pH units (p<0.02, n=11)