Temporary and partial inhibition of platelets by SM-20302 prevents coronary artery thrombosis in a chronic canine model.

We proposed that temporary and partial platelet inhibition by a GPIIb/IIIa receptor antagonist, SM-20302, would provide sustained antithrombotic efficacy in a chronic model of coronary artery thrombosis. Instrumented, conscious dogs received vehicle (Group I, n = 7), low dose SM-20302 (30 microg/kg bolus + 1 microg/kg/min infusion for 6 h) (Group II, n = 7), or high dose SM-20302 (100 microg/kg bolus + 1 microg/kg/min infusion for 6 h) (Group III, n = 7). Thrombosis was initiated by electrolytic injury to the circumflex coronary artery. Coronary blood flow was monitored for 6 h on day 1 and days 2-6. Platelet aggregation was performed in platelet-rich plasma prepared from citrated or heparinized blood. At 6 h, both doses of SM-20302 inhibited adenosine diphosphate-induced platelet aggregation completely (> 90%) in citrated platelet-rich plasma, but incompletely (57-59%) in heparinized platelet-rich plasma. Platelet reactivity returned to baseline values at 24 h. Control animals developed thrombotic occlusion on Day 1. Both doses of SM-20302 maintained vessel patency during the infusion period (Day 1) and the subsequent 5 days. Myocardial infarct size and mortality in the drug treated groups were reduced compared to the vehicle group. Thus, temporary inhibition of platelet reactivity by SM-20302 is associated with sustained prevention of primary thrombus formation, and reduction in infarct size and mortality.