Inhibition of thrombin attenuates stenosis after arterial injury in minipigs

Dana R. Abendschein, Dino Recchia, Yuan Yuan Meng, Luigi Oltrona, Samuel A. Wickline, Paul R. Eisenberg

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Objectives. We sought to determine whether brief, profound inhibition of thrombin or prothrombin activation by factor Xa limits neointimal formation and stenosis after arterial injury. Background. 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. Methods. 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. Results. 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-treated pigs (p <0.02 for r-hirudin vs. heparin treatment). Conclusions. The marked reduction of stenosis in r-hirudin-treated animals indicates that thrombin plays a major role in neointimal formation after balloon-induced arterial injury. A relatively brief interval of profound, direct inhibition of thrombin may be particularly effective to attenuate restenosis after balloon angioplasty.

Original languageEnglish
Pages (from-to)1849-1855
Number of pages7
JournalJournal of the American College of Cardiology
Volume28
Issue number7
DOIs
Publication statusPublished - Dec 1997

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Hirudins
Miniature Swine
Thrombin
Pathologic Constriction
Heparin
Factor Xa
Wounds and Injuries
Anticoagulants
Atherogenic Diet
Balloon Angioplasty
Partial Thromboplastin Time
Prothrombin
Hypercholesterolemia
Angioplasty
Carotid Arteries
Swine
Body Weight

ASJC Scopus subject areas

  • Nursing(all)

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Inhibition of thrombin attenuates stenosis after arterial injury in minipigs. / Abendschein, Dana R.; Recchia, Dino; Meng, Yuan Yuan; Oltrona, Luigi; Wickline, Samuel A.; Eisenberg, Paul R.

In: Journal of the American College of Cardiology, Vol. 28, No. 7, 12.1997, p. 1849-1855.

Research output: Contribution to journalArticle

Abendschein, Dana R. ; Recchia, Dino ; Meng, Yuan Yuan ; Oltrona, Luigi ; Wickline, Samuel A. ; Eisenberg, Paul R. / Inhibition of thrombin attenuates stenosis after arterial injury in minipigs. In: Journal of the American College of Cardiology. 1997 ; Vol. 28, No. 7. pp. 1849-1855.
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abstract = "Objectives. We sought to determine whether brief, profound inhibition of thrombin or prothrombin activation by factor Xa limits neointimal formation and stenosis after arterial injury. Background. 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. Methods. 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. Results. 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-treated pigs (p <0.02 for r-hirudin vs. heparin treatment). Conclusions. The marked reduction of stenosis in r-hirudin-treated animals indicates that thrombin plays a major role in neointimal formation after balloon-induced arterial injury. A relatively brief interval of profound, direct inhibition of thrombin may be particularly effective to attenuate restenosis after balloon angioplasty.",
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AU - Recchia, Dino

AU - Meng, Yuan Yuan

AU - Oltrona, Luigi

AU - Wickline, Samuel A.

AU - Eisenberg, Paul R.

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