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 thrombosis animal model with low flow conditions in the venous blood stream and then evaluate this model for testing new anticoagulants. In this model, the vena cava of rats was narrowed with a Doppler flow probe, blood flow velocity continuously recorded and thrombus formation initiated by thromboplastin infusion. Sixty-five minutes following thromboplastin infusion the animals were sacrificed and the following parameters measured: thrombus wet weight, fibrinopeptide A (FpA), activated partial thromboplastin time and platelet number. The new model was evaluated with aspirin, a PGI2 mimetic, heparin and a soluble thrombomodulin analogue. Without thromboplastin infusion no thrombus formation or reduction of blood flow was observed. Controls receiving thromboplastin infusion developed a thrombus, blood flow was arrested, platelet number 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 agents were not effective. This study demonstrates that, under low flow conditions, only a combination of blood flow reduction with a hypercoagulable state results in venous thrombus formation. This improved model of venous thrombosis more closely resembles the clinical situation and is applicable for testing anticoagulants.
Fredrich
M
M
Research Laboratories of Schering AG, Berlin, Germany.
Zierz
R
R
Morser
J
J
Wydro
R
R
Witt
W
W
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001783:Blood Flow Velocity; D003250:Constriction; D004195:Disease Models, Animal; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011465:Prostaglandins, Synthetic / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D018180:Thrombomodulin / Q000502:physiology; D013924:Thrombophlebitis / Q000503:physiopathology*; D013925:Thromboplastin / Q000494:pharmacology; D014682:Vena Cava, Inferior
D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors; D011465:Prostaglandins, Synthetic; D011994:Recombinant Proteins; D018180:Thrombomodulin; C088784:ZK 157138; D006493:Heparin; D013925:Thromboplastin; D011464:Epoprostenol; C043867:cicaprost; D001241:Aspirin