Inhibition of tissue factor-mediated coagulation markedly attenuates stenosis after balloon-induced arterial injury in minipigs

Luigi Oltrona, Christopher M. Speidel, Dino Recchia, Samuel A. Wickline, Paul R. Eisenberg, Dana R. Abendschein

Research output: Contribution to journalArticle

Abstract

Background: Exposure and upregulation of tissue factor in the wall of balloon-injured arteries may result in prolonged activation of coagulation contributing to restenosis. This study was designed to determine whether brief or more prolonged inhibition of tissue factor-mediated coagulation with tissue factor pathway inhibitor (TFPI) attenuates neointimal formation and luminal stenosis after balloon-induced arterial injury. Methods and Results: The carotid artery of minipigs fed an atherogenic diet was injured by repetitive balloon hyperinflations, a procedure that rapidly yields complex, plaque-like neointimal lesions and high-grade luminal stenosis. Recombinant TFPI (rTFPI) was administered intravenously beginning 15 minutes before balloon injury as either a high dose (0.5 mg/kg bolus and 100 μg·kg - 1·min -1) for 3 hours (n=7) or 24 hours (n=6) or as a low dose (0.5 mg/kg and 25 μg·kg -1·min -1) for 24 hours (n=6). Control animals received intravenous heparin (100 U·kg -1·h -1) for 3 hours (n=6) or 24 hours (n=7) or aspirin (5 mg/kg PO) followed by heparin for 24 hours (n=7). Luminal stenosis, assessed histologically 4 weeks after injury, was 73±17% and 76±18% (mean±SEM) in animals that received rTFPI or heparin for 3 hours, respectively. In contrast, luminal stenosis was only 11 ± 12% and 6 ± 3% in pigs given high and low doses, respectively, of rTFPI for 24 hours compared with 46 ± 22% in pigs given heparin for 24 hours and 40 ± 19% in those given both heparin and aspirin (P

Original languageEnglish
Pages (from-to)646-652
Number of pages7
JournalCirculation
Volume96
Issue number2
Publication statusPublished - Jul 15 1997

Keywords

  • Angioplasty
  • Coagulation
  • Stenosis
  • Thrombosis

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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    Oltrona, L., Speidel, C. M., Recchia, D., Wickline, S. A., Eisenberg, P. R., & Abendschein, D. R. (1997). Inhibition of tissue factor-mediated coagulation markedly attenuates stenosis after balloon-induced arterial injury in minipigs. Circulation, 96(2), 646-652.