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.