Sustained accumulation of 111 Indium-labelled platelets is induced in the cerebral vasculature of rabbits by bolus intracarotid (i.c.) administration of thrombin. Bolus i.c. injection of the thrombin inhibitor Argatroban, 1 min before thrombin, produced reductions in platelet accumulation of up to more than 90% whereas when administered 1 min after thrombin there was no significant effect. Intracarotid infusion of Argatroban (at dose effective when administered prior to thrombin), commencing 30 min after thrombin, produced no significant reduction in entrapped platelets. Argatroban did not enhance the ability of infusion of a threshold dose of rt-PA to decrease an established cerebrovascular thrombosis. These results suggest that pretreatment with thrombin-inhibitor, Argatroban can inhibit thrombin-induced cerebral thromboembolism in the rabbits and cannot enhance the profibrinolytic effect of rt-PA.
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