Summary
Protein C is the key component in a natural anticoagulant pathway. After its activation
by the thrombin-thrombomodulin complex, it degrades the activated forms of coagulation
cofactors VIII and V, which leads to downregulation of the coagulation process. Due
to its specific anticoagulant activity, activated protein C (APC) is potentially interesting
as an antithrombotic agent. The effect of bovine activated protein C on thrombus formation
and haemostasis was investigated in a rabbit model of microarterial thrombosis. Segments
of both central ear arteries were prepared and blood-flow interrupted with double
vascular clamps.
Longitudinal arteriotomies (7 mm) and deep vessel wall trauma (5 mm) were performed,
whereafter the arteriotomies were closed with running sutures. Five minutes prior
to opening of the clamps (reperfusion), boluses of APC (0.8 mg/kg body weight) or
vehicle alone were administered to two groups, each of 10 rabbits, in a blind random
fashion. Vessel patency-rates were drastically improved by the administration of APC
compared to vehicle. Correspondingly, thrombus weights were significantly lower in
the APC group than in the control group. The activated partial thromboplastin time
was prolonged to approximately twice the baseline throughout the 2 h observation interval
in the APC group. Levels of circulating platelets were unaffected by the APC infusion,
but the arteriotomy bleeding times were significantly longer in the APC group. In
summary, activated protein C exerted powerful and long-acting antithrombotic effects
in a microarterial model of thrombosis in rabbits.
