© 2002 by European Society of Cardiology
Copyright © 2002, European Society of Cardiology
Thrombostatin, a bradykinin metabolite, reduces platelet activation in a model of arterial wall injury
aDepartment of Internal Medicine, Divisions of Cardiology and Hematology and Oncology, Michigan State University, East Lansing, MI, USA
bDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
cThromgen, Inc., Ann Arbor, MI, USA
* Corresponding author. Present address: Department of Medicine/Cardiology, Michigan State University, B-208 Clinical Center, East Lansing, MI 48824, USA. Tel.: +1-517-353-4832; fax: +1-517-432-4039 abela{at}pilot.msu.edu
Objective: Thrombin activates platelets and contributes to the occlusion of arteries following thrombolytic therapy or angioplasty. Thrombostatin (RPPGF), the angiotensin converting enzyme degradation product of bradykinin, inhibits 
-thrombin induced platelet activation. We hypothesized that thrombostatin prevents platelet aggregation and adhesion after balloon angioplasty (BA). Methods: Platelet-rich plasma (PRP) was obtained from 22 Beagle dogs before sacrifice and 10% of the PRP was labeled with 111In. Carotid arteries were then removed from each dog and mounted in a dual perfusion chamber and intimal injury was performed with BA. 111In-PRP with or without thrombostatin or aspirin alone was perfused through the arteries for 60 min. During perfusion, platelet volume was measured using a Coulter counter and a laser-light scattering technique. Platelet adhesion to arteries was measured by radioactivity count. Results: Arterial injury alone compared to non-injury increased platelet volume in the circuit by 1.4 times (x) (P<0.05) using a Coulter counter or 1.8x (P<0.05) using laser-light scattering and increased platelet adhesion by 2.3x (P<0.01). When compared to BA injury alone, the addition of thrombostatin reduced platelet volume by 1.8x (P<0.03) as measured by Coulter counter or 1.9x (P<0.01) by laser-light scattering and platelet adhesion by 4.2x (P<0.05). Compared to BA injury alone, aspirin reduced platelet volume by 1.2x (P<0.01) as assessed by Coulter counter or 1.5x (P<0.03) using laser-light scattering and platelet adhesion by 1.8x (P<0.02). Conclusion: Thrombostatin or aspirin independently decreases evidence of platelet activation in the canine carotid artery model of BA injury.
KEYWORDS Angioplasty; Anticoagulants; Arteries; Platelets; Thrombosis/embolism
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