Effect of inhibitors of factor Xa or platelet adhesion, heparin, and aspirin on platelet deposition in an atherosclerotic rabbit model of angioplasty injury.
Acute thrombotic reocclusion and restenosis after successful coronary angioplasty are limitations of the procedure. Although the restenotic process is not completely understood, acute platelet deposition and thrombosis are considered important initiating mechanisms. The effort to identify pharmacologic agents capable of modifying acute platelet action following mechanical injury requires an animal model mimicking the clinical pathophysiology as closely as possible. We developed a model of angioplasty-induced injury in atherosclerotic rabbit femoral arteries. Acute 111indium-labelled platelet deposition and thrombosis were assessed four hours after balloon-injury in arteries subjected to prior endothelial damage (air desiccation) and cholesterol supplementation (one month). The effects of recombinant tick anticoagulant peptide (rTAP), a blood coagulation factor Xa (fXa) inhibitor and of recombinant leech antiplatelet protein (rLAPP), a platelet adhesion inhibitor, were compared to heparin (HEP) and aspirin (ASA). Recombinant TAP and HEP, but not rLAPP or ASA, successfully prevented thrombus formation and reduced platelet deposition in balloon-injured vessel segments to levels not significantly different from those observed in the contralateral atherosclerotic non-balloon-injured vessels. Therefore, this model, incorporating balloon catheter dilation of arteries exhibiting neointimal growth and atherosclerotic plaque formation, may be useful for evaluation of possible adjunctive therapies during angioplasty.
Lyle
E M
EM
Department of Pharmacology, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
Fujita
T
T
Conner
M W
MW
Connolly
T M
TM
Vlasuk
G P
GP
Lynch
J L
JL
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D000818:Animals; D001161:Arteriosclerosis / Q000473:pathology*; D060829:Arthropod Proteins; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects*; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D065427:Factor Xa Inhibitors; D006493:Heparin / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D010455:Peptides / Q000494:pharmacology; D010973:Platelet Adhesiveness / Q000187:drug effects; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D012471:Salivary Proteins and Peptides / Q000494:pharmacology; D013927:Thrombosis / Q000473:pathology
D060829:Arthropod Proteins; D065427:Factor Xa Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; C073760:LAPP protein, Haementeria officinalis; D010455:Peptides; D011994:Recombinant Proteins; D012471:Salivary Proteins and Peptides; C063967:tick anticoagulant peptide; D006493:Heparin; D001241:Aspirin