THROMBIN INHIBITORS AND ANTI-COAGULANTS ON THROMBIN-INDUCED EMBOLIZATION IN RABBIT CRANIAL VASCULATURE

(111)Indium-labelled platelets were continuously monitored in the cran ial vasculature of anaesthetised rabbits and thrombin inhibitors and a nti-coagulants were tested on the sustained platelet accumulation indu ced by intracarotid injection of thrombin (90 U/kg). Pretreatment, com mencing 30 min prior to thrombin, with a I-h intracarotid infusion of D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone (PPACK; 0.25-1. 0 mu g/kg per min), unfractionated heparin (Multiparin; 5-20 U/kg bolu s + 0.75-3.0 U/kg per min infusion) or low molecular weight heparin (F ragmin; 2.4-9.6 U/kg per min) produced dose-related reductions in plat elet accumulation. Continuous infusion of acetyl-D-phenylalanyl-prolyl -boroarginine (DuP-714 ester; 30 mu g/kg per min) for 30 min induced m arked accumulation of platelets in the pulmonary circulation in the ab sence of thrombin. Bolus intracarotid injection, 1 min before thrombin , of Hirulog (0.05-0.2 mg/kg), PPACK (10-30 mu g/kg), Multiparin (25-1 00 U/kg), Fragmin (150 U/kg) or DuP-714 ester (15-30 mu g/kg) caused s ignificant reductions in platelet accumulation. When injected 1 min af ter thrombin, Hirulog (1 mg/kg), PPACK (100 mu g/kg), Fragmin (150 U/k g) and DuP-714 ester (30 mu g/kg) had no significant effect and Multip arin (100 U/kg) increased platelet accumulation. The results demonstra te that pretreatment with a range of thrombin inactivators, acting via different mechanisms, can inhibit thrombin-induced cerebral thromboem bolism in the rabbit.