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Thromb Haemost 2001; 86(05): 1296-1304
DOI: 10.1055/s-0037-1616065
Review Article
Schattauer GmbH

Thrombostatin Inhibits Cyclic Flow Variations in Stenosed Canine Coronary Arteries

Ahmed A. K. Hasan
1   Hematology/Oncology, Ann Arbor, MI, USA
6   Thromgen, Inc., Ann Arbor, MI, USA
,
Alvin H. Schmaier
1   Hematology/Oncology, Ann Arbor, MI, USA
4   Pathology, Ann Arbor, MI, USA
6   Thromgen, Inc., Ann Arbor, MI, USA
,
Mark Warnock
6   Thromgen, Inc., Ann Arbor, MI, USA
,
Daniel Normolle
5   Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI
,
Edward Driscoll
3   Pharmacology, Ann Arbor, MI, USA
,
Benedict R. Lucchesi
3   Pharmacology, Ann Arbor, MI, USA
,
Steven W. Werns
2   Cardiology Divisions, Departments of Internal Medicine, Ann Arbor, MI, USA
› Author AffiliationsThe worked was supported by NIH grant HL56415 to Dr. Schmaier and grants HL61081 and HL61981 to Dr. Hasan.
Further Information

Publication History

Received 06 October 2000

Accepted after resubmission 22 June 2001

Publication Date:
13 December 2017 (online)

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Summary

Thrombostatins are a group of compounds based upon a breakdown product of bradykinin, RPPGF. They inhibit -thrombin-induced platelet activation by binding to protease activated receptor 1 and, at a lower affinity, by interacting with thrombin’s active site. After a single intravenous infusion of MAP4-RPPGF (11.58 mg/kg), its t½α was 4.5 min with a clearance of 2.0 ml/min. MAP4-RPPGF administration had a sustained antiplatelet effect, preventing γ-thrombin-induced (12.5 nM) platelet activation for 4 h. Its antiplatelet effect summated with that of aspirin and/or clopidogrel. MAP4-RPPGF was compared with aspirin and clopidogrel in the Folts model of coronary artery thrombosis. Dogs were randomized to 3 treatment groups: aspirin 1.14 mg/kg i. v., clopidogrel 0.5 mg/kg i. v., or MAP4-RPPGF 0.77 mg/kg i. v. Cyclic flow variations (CFV) were recorded in 5 untreated dogs hourly for 3 successive hours and for 1 h before (all groups >11 CFV/h), and for 2 h after drug infusion in each of the 3 treatment groups. After 1 h drug treatment, all groups of animals had <6 CFV/h; after 2 h treatment, all had <1 CFV/h. All agents significantly reduced CFV from control at each hour, but none was significantly better than any other. Thrombostatin was as effective as aspirin or clopidogrel in inhibiting coronary artery thrombosis in this canine model.

Keywords

Thrombin - platelets - coronary thrombosis - bradykinin - thrombostatin
 

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