Summary
Endogenously activated protein C is evaluated for antithrombotic activity in porcine
carotid arteries subjected to mechanical trauma. Protein C is activated by intravenous
administration of guanidinobenzoyl- thrombin, which binds to thrombomodulin and there
deacylates to yield thrombin. The bound, transiently active thrombin yields a peak
of anticoagulant activity between 5 and 10 min after infusion of the latent thrombin.
Inhibition of thrombin binding in vivo by co-infusing an active-site-blocked thrombin
preparation elicits acute and lethal systemic thrombosis. Nearly occlusive platelet
thrombosis, which occurs within 30 min of crushing 1 cm segments of carotid arteries
with a standard hemostat, is blocked by endogenous protein C activation initiated
2 min before the crush injury. It is concluded that activated protein C blocks thrombosis
in deeply injured musculo-elastic arteries, and that activation of latent thrombin
bound to thrombomodulin in vivo is a practical means for delivery of pharmacologically
effective concentrations of activated protein C.
