Two 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 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 alpha-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 anti-coagulants, as is venous thrombosis.
Vogel
G M
GM
Scientific Development Group, N.V. Organon, Oss, The Netherlands.
van Amsterdam
R G
RG
Zandberg
P
P
van Houwelingen
P
P
Kop
W J
WJ
van Mensvoort
F W
FW
Meuleman
D G
DG
D000818:Animals; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013917:Thrombin; D013927:Thrombosis / Q000188:drug therapy
D005343:Fibrinolytic Agents; D013917:Thrombin