title: Thrombostatin, a bradykinin metabolite, reduces platelet activation in a model of arterial wall injury.
abstract: 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 alpha-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).
  
  
  CONCLUSIONS
  Thrombostatin or aspirin independently decreases evidence of platelet activation in the canine carotid artery model of BA injury.
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Alejandro R
authors.initials: AR
authors.lastname: Prieto
authors.forename: Hongbao
authors.initials: H
authors.lastname: Ma
authors.forename: Ruiping
authors.initials: R
authors.lastname: Huang
authors.forename: Gauhar
authors.initials: G
authors.lastname: Khan
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Schwartz
authors.forename: Elie E
authors.initials: EE
authors.lastname: Hage-Korban
authors.forename: Alvin H
authors.initials: AH
authors.lastname: Schmaier
authors.forename: John M
authors.initials: JM
authors.lastname: Davis
authors.forename: Ahmed A K
authors.initials: AA
authors.lastname: Hasan
authors.forename: George S
authors.initials: GS
authors.lastname: Abela
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000473:pathology; D001920:Bradykinin / Q000378:metabolism* / Q000494:pharmacology*; D002339:Carotid Arteries / Q000648:ultrastructure; D020212:Carotid Artery Injuries / Q000209:etiology / Q000473:pathology*; D016893:Carotid Stenosis / Q000628:therapy; D002404:Catheterization / Q000009:adverse effects*; D048429:Cell Size / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D007834:Lasers; D008855:Microscopy, Electron, Scanning; D019007:P-Selectin / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D012542:Scattering, Radiation
chemical_list: D019007:P-Selectin; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; C079000:bradykinin (1-5); D001241:Aspirin; D001920:Bradykinin