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Thromb Haemost 1995; 74(03): 879-885
DOI: 10.1055/s-0038-1649841
Original Article
Coagulation
Schattauer GmbH Stuttgart

Antithrombotic Action of Endogenous Porcine Protein C Activated with a Latent Porcine Thrombin Preparation

Robert D McBane
1   The Division of Cardiovascular Diseases and Internal Medicine, Rochester, MN, USA
2   The Section of Hematology Research, Rochester, MN, USA
,
Waldemar E Wysokinski
1   The Division of Cardiovascular Diseases and Internal Medicine, Rochester, MN, USA
2   The Section of Hematology Research, Rochester, MN, USA
,
James H Chesebro
1   The Division of Cardiovascular Diseases and Internal Medicine, Rochester, MN, USA
,
Whyte G Owen
2   The Section of Hematology Research, Rochester, MN, USA
3   The Departments of Biochemistry and Molecular Biology, Mayo Foundation for Education and Research, Rochester, MN, USA
› Author Affiliations
Further Information

Publication History

Received 09 February 1995

Accepted after resubmission 23 May 1995

Publication Date:
09 July 2018 (online)

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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.

 

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