A NEW ANIMAL-MODEL OF VENOUS THROMBOSIS IN RATS WITH LOW-FLOW CONDITIONS IN THE VENOUS-BLOOD STREAM

The aims of the present investigation were to develop a new venous thr ombosis animal model with low flow conditions in the venous blood stre am and then evaluate this model for testing new anticoagulants. In thi s model, the vena cava of rats was narrowed with a Doppler flow probe, blood flow velocity continuously recorded and thrombus formation init iated by thromboplastin infusion. Sixty-five minutes following thrombo plastin infusion the animals were sacrificed and the following paramet ers measured: thrombus wet weight, fibrinopeptide A (FpA), activated p artial thromboplastin time and platelet number. The new model was eval uated with aspirin, a PGI(2) mimetic, heparin and a soluble thrombomod ulin analogue. Without thromboplastin infusion no thrombus formation o r reduction of blood flow was observed. Controls receiving thromboplas tin infusion developed a thrombus, blood flow was arrested, platelet n umber decreased and FpA was elevated. In contrast, animals pretreated with anticoagulants maintained a residual flow, while thrombus weight, thrombocytopenia and FpA elevation were reduced. The antiplatelet age nts were not effective. This study demonstrates that, under low flow c onditions, only a combination of blood flow reduction with a hypercoag ulable state results in venous thrombus formation. This improved model of venous thrombosis more closely resembles the clinical situation an d is applicable for testing anticoagulants.