|
| HOME | SUBSCRIPTIONS | CURRENT ISSUE | PAST ISSUES | CARDIOSOURCE | SEARCH | HELP | FEEDBACK |
|
|
|
|||||||||
|
|||||||||||
|
J Am Coll Cardiol, 1996; 28:1849-1855 © 1996 by the American College of Cardiology Foundation |
Department of Internal Medicine, Washington University School of Medicine, Saint Louis, Missouri 63110, USA.
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.
This article has been cited by other articles:
|
|
 |
|
  F. Bea, J. Kreuzer, M. Preusch, S. Schaab, B. Isermann, M. E. Rosenfeld, H. Katus, and E. Blessing Melagatran Reduces Advanced Atherosclerotic Lesion Size and May Promote Plaque Stability in Apolipoprotein E- Deficient Mice Arterioscler. Thromb. Vasc. Biol., December 1, 2006; 26(12): 2787 - 2792. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. G. Touchard and R. S. Schwartz Preclinical Restenosis Models: Challenges and Successes Toxicol Pathol, January 1, 2006; 34(1): 11 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Schwartz, N. A. Chronos, and R. Virmani Preclinical restenosis models and drug-eluting stents: Still important, still much to learn J. Am. Coll. Cardiol., October 6, 2004; 44(7): 1373 - 1385. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Tokunou, T. Ichiki, K. Takeda, Y. Funakoshi, N. Iino, and A. Takeshita cAMP Response Element-Binding Protein Mediates Thrombin-Induced Proliferation of Vascular Smooth Muscle Cells Arterioscler. Thromb. Vasc. Biol., November 1, 2001; 21(11): 1764 - 1769. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Patterson, G. A. Stouffer, N. Madamanchi, and M. S. Runge New Tricks for Old Dogs : Nonthrombotic Effects of Thrombin in Vessel Wall Biology Circ. Res., May 25, 2001; 88(10): 987 - 997. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-m. Cheung, M. R. D’Andrea, P. Andrade-Gordon, and B. P. Damiano Altered Vascular Injury Responses in Mice Deficient in Protease-Activated Receptor-1 Arterioscler. Thromb. Vasc. Biol., December 1, 1999; 19(12): 3014 - 3024. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. St. Pierre, L.-Y. Yang, K. Tamirisa, D. Scherrer, P. De Ciechi, P. Eisenberg, E. Tolunay, and D. Abendschein Tissue Factor Pathway Inhibitor Attenuates Procoagulant Activity and Upregulation of Tissue Factor at the Site of Balloon-Induced Arterial Injury in Pigs Arterioscler. Thromb. Vasc. Biol., September 1, 1999; 19(9): 2263 - 2268. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Gallo, A. Padurean, V. Toschi, J. Bichler, J. T. Fallon, J. H. Chesebro, V. Fuster, and J. J. Badimon Prolonged Thrombin Inhibition Reduces Restenosis After Balloon Angioplasty in Porcine Coronary Arteries Circulation, February 17, 1998; 97(6): 581 - 588. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Oltrona, C. M. Speidel, D. Recchia, S. A. Wickline, P. R. Eisenberg, and D. R. Abendschein Inhibition of Tissue Factor–Mediated Coagulation Markedly Attenuates Stenosis After Balloon-Induced Arterial Injury in Minipigs Circulation, July 15, 1997; 96(2): 646 - 652. [Abstract] [Full Text]
|
|
| HOME | SUBSCRIPTIONS | CURRENT ISSUE | PAST ISSUES | CARDIOSOURCE | SEARCH | HELP | FEEDBACK |
