Effect of milrinone in human platelet shape change, aggregation and thromboxane A2 synthesis: an in vitro study

Milrinone (MIL; a cAMP-specific phosphodiesterase type-III inhibitor), added in vitro to achieve concentrations below the therapeutic levels, inhibited agonist-induced platelet shape change (PSC). Arachidonic acid (AA)-induced PSC was significantly more inhibited by a combination of MIL and indomethacin (INDO; a cyclooxygenase inhibitor) than by either alone. PSC induced by 5-hydroxytryptamine was inhibited by MIL but not by INDO; and this effect of MIL was not augmented by INDO. Whole blood-platelet aggregation (WB-PA) and platelet-rich plasma aggregation induced by potent stimulators of thromboxane A2 (TXA2) synthesis such as AA and calcium ionophore and by less potent agonists (e.g. ADP and U46619) were inhibited by MIL at or near therapeutic concentrations. WB-PA induced by collagen was significantly more inhibited by the MIL and INDO combination than by either of these agents alone whereas with ADP-induced WB-PA no additional effect could be shown when both MIL and INDO were co-incubated. MIL and similar types of drugs may be of benefit in conditions associated with platelet hyperactivity and some of these effects may be enhanced by cyclooxygenase inhibitors.