Inhibition of thrombin attenuates stenosis after arterial injury in minipigs

Journal of the American College of Cardiology
D R AbendscheinP R Eisenberg

Abstract

We sought to determine whether brief, profound inhibition of thrombin or prothrombin activation by factor Xa limits neointimal formation and stenosis after arterial injury. Thrombin has been implicated as a mediator of neointimal formation, but adjunctive administration of anticoagulant agents has not proven effective to decrease restenosis in patients undergoing coronary angioplasty. We infused recombinant desulfatohirudin (r-hirudin, bolus of 2 mg/kg body weight followed by 2 mg/kg per h, n = 9), heparin (100 U/kg per h, n = 6) or recombinant tick anticoagulant peptide (rTAP, 1-mg/kg bolus followed by 3 mg/kg per h, n = 5), a specific inhibitor of factor Xa, intravenously, beginning 15 min before and for up to 3 h after repetitive balloon hyperinflations sufficient to disrupt the internal elastic lamina in a carotid artery of minipigs with hypercholesterolemia induced by feeding them an atherogenic diet. Partial thromboplastin time was increased six- to sevenfold over baseline levels at the end of the infusions of the anticoagulant agents. Lumen stenosis measured histologically 4 weeks after balloon-induced carotid injury was 29 +/- 16% (mean +/- SEM) in r-hirudin-treated, 52 +/- 19% in rTAP-treated and 76 +/- 18% in heparin-...Continue Reading

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Citations

Dec 8, 2010·Canadian Journal of Anaesthesia = Journal Canadien D'anesthésie·Sunil X AnandPaul M Heerdt
May 18, 1999·International Journal of Cardiology·L O ViscontiA Pezzano
Mar 18, 2000·Cardiovascular Pathology : the Official Journal of the Society for Cardiovascular Pathology·M C WyersW C Quist
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Jul 23, 2003·Journal of Thrombosis and Haemostasis : JTH·D R AbendscheinJ St Pierre
Jul 5, 2005·Expert Opinion on Investigational Drugs·B KaiserJ Fareed
Jul 2, 2005·Expert Opinion on Investigational Drugs·L ChiK P Gallagher
Dec 1, 1996·Journal of the American College of Cardiology·G A Stouffer, M S Runge
Oct 7, 2004·Journal of the American College of Cardiology·Robert S SchwartzRenu Virmani
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Aug 11, 2020·Current Problems in Surgery·Morgan P McMonagle

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