2 NEW CLOSELY-RELATED RAT MODELS WITH RELEVANCE TO ARTERIAL THROMBOSIS - EFFICACIES OF DIFFERENT ANTITHROMBOTIC DRUGS

Two thrombosis models in rats are described in which mixed type thromb i are formed at arterial and venous flow rates. The models, containing a silk thread in the aorta and vena cava, respectively, were characte rised for the activity of three platelet inhibitors, three thrombin ac tive site inhibitors and five glycosaminoglycans (GAGs). In the two mo dels a similar highly platelet-dependent thrombus developed both in si ze and composition during the first 10 min after insertion of the silk thread. The thrombotic processes were self-limiting, thus maintaining blood flow, but persisted twice as long in the vena cava model. In bo th models the thrombus consisted for more than 65% of platelets. Throm bus development under arterial as well as under venous flow conditions was inhibited dose dependently by all tested compounds including aspi rin and the synthetic a-methyl glycoside copy of the ATIII binding pen tasaccharide within heparin, Org31540/SR90107A. Simultaneous fibrin de position and platelet activation, which represents an essential elemen t of arterial thrombosis, initially dominated in both models. The grad ual thrombus outgrowth, in the cava model, was more sensitive to facto r Xa selective anticoagulants, as is venous thrombosis.