Summary
Two thrombosis models in rats are described in which mixed type thrombi are formed
at arterial and venous flow rates. The models, containing a silk thread in the aorta
and vena cava, respectively, were characterised for the activity of three platelet
inhibitors, three thrombin active site inhibitors and five glycosaminoglycans (GAGs).
In the two models a similar highly platelet-dependent thrombus developed both in size
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 both models the thrombus consisted for more than 65%
of platelets. Thrombus development under arterial as well as under venous flow conditions
was inhibited dose dependently by all tested compounds including aspirin and the synthetic
α-methyl glycoside copy of the ATIII binding pentasaccharide within heparin, Org31540/SR90107A.
Simultaneous fibrin deposition and platelet activation, which represents an essential
element of arterial thrombosis, initially dominated in both models. The gradual thrombus
outgrowth, in the cava model, was more sensitive to factor Xa selective anticoagulants,
as is venous thrombosis.
