ADJUVANT EFFECT OF ARGATROBAN ON STAPHYLOKINASE INDUCED THROMBOLYSIS OF PLATELET-RICH THROMBI IN RAT MESENTERIC VENULES IN-VIVO

Effective, therapeutic thrombolysis should not only promote dissolutio n of fibrin but should also regulate continued thrombin-induced fibrin formation and the accumulation of platelets on the thrombotic lesion. The aim of the present study was to assess the use of a synthetic, lo w molecular weight thrombin inhibitor, argatroban in association with a well defined thrombolytic agent in a reproducible animal model of th rombolysis in vivo. Thrombi were formed in rat mesenteric venules with a helium neon (He-Ne) laser in the presence of Evans blue and were st abilised for 10 minutes. Thrombi formed in this manner were shown by t ransmission electron microscopy to be composed mainly of platelets. Th rombolysis was induced with recombinant staphylokinase in the presence and absence of argatroban and the process was monitored using compute rised image analysis. Go-infusion of argatroban at a dose of 2.0mg/kg/ h with staphylokinase significantly enhanced the rate of thrombolysis. The results suggested that administration of the thrombin inhibitor t ogether with the fibrinolytic agent moderated platelet-dependent mecha nisms and led to a more rapid restoration of blood vessel patency. (C) 1997 Elsevier Science Ltd.