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 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.
Prieto
Alejandro R
AR
Department of Internal Medicine, Division of Cardiology, Michigan State University, East Lansing, MI 48824, USA.
Ma
Hongbao
H
Huang
Ruiping
R
Khan
Gauhar
G
Schwartz
Kenneth A
KA
Hage-Korban
Elie E
EE
Schmaier
Alvin H
AH
Davis
John M
JM
Hasan
Ahmed A K
AA
Abela
George S
GS
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
D019007:P-Selectin; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; C079000:bradykinin (1-5); D001241:Aspirin; D001920:Bradykinin