Thrombostatin, a bradykinin metabolite, reduces platelet activation in a model of arterial wall injury

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 α-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 (×) ( P <0.05) using a Coulter counter or 1.8× ( P <0.05) using laser-light scattering and increased platelet adhesion by 2.3× ( P <0.01). When compared to BA injury alone, the addition of thrombostatin reduced platelet volume by 1.8× ( P <0.03) as measured by Coulter counter or 1.9× ( P <0.01) by laser-light scattering and platelet adhesion by 4.2× ( P <0.05). Compared to BA injury alone, aspirin reduced platelet volume by 1.2× ( P <0.01) as assessed by Coulter counter or 1.5× ( P <0.03) using laser-light scattering and platelet adhesion by 1.8× ( P <0.02). Conclusion: Thrombostatin or aspirin independently decreases evidence of platelet activation in the canine carotid artery model of BA injury.