Antithrombotic effects of three thrombin inhibitors in a rat model of laser-induced thrombosis

The antithrombotic effects of three thrombin inhibitors (hirudin, NAPAP and argidipine) were investigated in an experimental thrombosis model using laser lesions of rat mesenteric venules. Furthermore, their in vitro anticoagulant activity (partial thromboplastin time, thrombin time, Heptest, inhibition of factor IIa and factor Xa) in human platelet poor plasma (PPP) and their in vitro and ex vivo activities were studied in rat plasma. All three thrombin inhibitors showed significant and dose-dependent antithrombotic effects after intravenous injection, if venules were damaged, which lasted for more than 4 but less than 8 h. The anticoagulant effect observed in vitro did not differ much between human and rat PPP. The two synthetic thrombin inhibitors NAPAP and argidipine were about as effective as hirudin in vitro; however, the ex vivo effect after intravenous injection of hirudin in rats was more pronounced than that observed with the two synthetic thrombin inhibitors. The antithrombotic effect of all three thrombin inhibitors in the laser model lasted much longer than the anticoagulant activity. This fact needs further investigations in the future.