Antithrombotic action of endogenous porcine protein C activated with a latent porcine thrombin preparation.
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 and 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 is 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.
McBane
R D
RD
Division of Cardiovascular Diseases, Mayo Foundation for Education and Research, Rochester, MN 55905, USA.
Wysokinski
W E
WE
Chesebro
J H
JH
Owen
W G
WG
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D020212:Carotid Artery Injuries; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D006629:Hirudins / Q000494:pharmacology*; D010976:Platelet Count / Q000187:drug effects; D011486:Protein C / Q000187:drug effects*; D013552:Swine; D013917:Thrombin / Q000494:pharmacology*
D000925:Anticoagulants; D005343:Fibrinolytic Agents; D006629:Hirudins; D011486:Protein C; D006493:Heparin; D013917:Thrombin