Wire-Coil Induced Thrombosis

PURPOSE AND RATIONALE A classical method to produce thrombosis is based on the insertion of wire coils into the lumen of blood vessels. The model was first described by Stone and Lord (1951) in an aorta of a dog and was further modified to be used in arterial coronary vessels of opened-chest dogs. The use in venous vessels was described by Kumada et al. (1980). 

The formation of thrombotic material around the coil is reproducible and can be easily standardized to study pharmacological agents (Just and Schonafinger 1991a Mellott et al. 1993 Rubsamen and Homberger 1996). 

Venous thrombosis is produced in rats by insertion of a stainless steel wire coil into the inferior caval vein. Platelets as well as plasmatic coagulation are activated on the wire coil. Thrombus formation onto the wire is quantitated by measuring the protein content of the thrombotic material isolated. The kinetics of thrombus formation show an increase in weight and protein content within the first 30 min followed by a steady state between thrombus formation and endogenous thrombolysis leading to a constant protein content of thrombi between 1 and up to 48 h following implantation of the wire coil. Thrombosis incidence in untreated control animals in this model is 100%. The test is used to evaluate antithrombotic and thrombolytic properties of compounds in an in vivo-model of venous thrombosis in rats. 

Male Sprague-Dawley rats weighing 260-300 g receive the test compound or the vehicle (controls) by oral, intravenous or intraperitoneal administration. At the end of absorption (i.v. 1 min, i.p. 30 min, p.o. 60 min), the animals are anesthetized by in- 

In addition to the described preparation, for continuous infusion of a thrombolytic test solution a polyethylene catheter is inserted in the jugular vein. One and a half hours after implantation of the wire coil, the test compound or the vehicle (controls) is infused for up to 2.5 h. The wire coil is then removed and the protein content of thrombi is determined (see above). Bernat et al. (1986) demonstrated the fibrinolytic activity of urokinase and streptokinase-human plasminogen complex in this model. 

---