A highly reproducible model of arterial thrombosis in rats

The objective of this investigation was to develop a reproducible and reliable method of arterial thrombosis in a small laboratory animal. Rats were anesthetized with urethane, and a common carotid artery was exposed. A completely occlusive thrombus was produced by applying an electric current to the arterial wall (2 mA for 5 min) while simultaneously constricting the artery with a hemostatic clamp placed immediately downstream from the electrodes. A complete and persistent cessation of blood flow was obtained in all the control rats starting 10-15 min after the thrombogenic lesion. Histological examination revealed a picture of mixed white and red thrombus, stratified and rich in platelets aggregates and fibrin, with piles of red cells trapped in the fibrin network. On the other hand, stasis alone (clamping) was ineffective at all, whereas electric current application alone caused non-occlusive thrombosis only in 30% of animals. An antithrombotic dose of heparin (3 mg/kg i.v., 30 min before thrombus induction) prevented the formation of a persistent thrombus, blood flow being progressively restored (up to 59% of basal value within 45 min). Similarly, a thrombolytic dose of urokinase-type plasminogen activator (2 mg/kg, for 120 min, starting 15 min after thrombus induction) caused a rapid and progressive resumption of blood flow (up to 80% of basal value). This method gives highly consistent and reproducible results and may be suitable for the study or the screening of antithrombotic as well as thrombolytic agents.