Thrombostatin inhibits cyclic flow variations in stenosed canine coronary arteries

Thrombostatins are a group of compounds based upon a breakdown product of b radykinin, RPPGF They inhibit a-thrombin-induced platelet activation by bin ding to protease activated receptor I and, at a lower affinity, by interact ing with thrombin's active site. After a single intravenous infusion of MAP 4-RPPGF (11.58 mg/kg), its t(1/2)alpha was 4.5 min with a clearance of 2.0 ml/min. MAP4-RPPGF administration had a sustained antiplatelet effect, prev enting gamma -thrombin-induced (12.5 nM) platelet activation for 4 h. Its a ntiplatelet effect summated with that of aspirin and/or clopidogrel. MAP4-R PPGF was compared with aspirin and clopidogrel in the Folts model of corona ry artery thrombosis. Dogs were randomized to 3 treatment groups: aspirin 1 .14 mg/kg i. v., clopidogrel 0.5 mg/kg i. v., or MAP4-RPPGF 0.77 mg/kg i. v . Cyclic flow variations (CFV) were recorded in 5 untreated dogs hourly for 3 successive hours and for 1 h before (all groups > 11 CFV/h), and for 2 h after drug infusion in each of the 3 treatment groups. After I h drug trea tment, all groups of animals had <6 CFV/h; after 2 h treatment, all had <1 CFV/h All agents significantly reduced CFV from control at each hour. but n one was significantly better than any other. Thrombostatin was as effective as aspirin or clopidogrel in inhibiting coronary artery thrombosis in this canine model.