Document Detail

Effectiveness of recombinant desulphatohirudin in reducing restenosis after balloon angioplasty of atherosclerotic femoral arteries in rabbits.
MedLine Citation:
PMID:  1829399     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: The effectiveness of balloon angioplasty is limited by a restenosis rate of approximately 30%. Recombinant desulphatohirudin (r-hirudin [CGP 39393]) has been found to be highly effective in preventing acute platelet-rich thrombosis after deep arterial injury as compared with heparin. METHODS AND RESULTS: This study evaluated the effect of intravenous r-hirudin, a selective inhibitor of thrombin, on restenosis after balloon angioplasty in 29 rabbits. Focal femoral atherosclerosis was induced by air desiccation endothelial injury followed by a 2% cholesterol diet for 1 month. At angioplasty (2.5-mm balloon with three 60-second, 10-atm inflations 60 seconds apart), the rabbits received heparin (150 units/kg bolus, n = 16) or r-hirudin (1 mg/kg bolus followed by infusions of 1 mg/kg for the first hour and 0.5 mg/kg for the second hour, n = 13). Angiograms performed before and after angioplasty and before death were analyzed quantitatively by a blinded observer. Rabbits were killed 2 hours (n = 14) or 28 days (n = 15) after angioplasty. Femoral arteries were fixed in situ by perfusion of 10% formaldehyde at 100 mm Hg. The mean luminal diameter of the arteries with successful angioplasty (greater than or equal to 20% increase in luminal diameter) in rabbits treated with heparin (n = 8 arteries) increased from 1.18 +/- 0.29 mm before angioplasty to 1.86 +/- 0.24 mm immediately after angioplasty (p less than 0.001) and decreased to 0.94 +/- 0.69 mm (p = 0.0004) at 28 days after angioplasty. In rabbits treated with r-hirudin (n = 11 arteries), the mean luminal diameter increased from 1.14 +/- 0.17 mm before angioplasty to 1.68 +/- 0.20 mm immediately after angioplasty (p less than 0.001) and decreased to 1.37 +/- 0.47 mm (p = 0.01) at 28 days after angioplasty. The mean reduction in luminal diameter by angiography was less in the r-hirudin-treated group than in the heparin-treated group (0.30 +/- 0.33 versus 0.92 +/- 0.61 mm, p = 0.01). Blinded planimetric analysis of stained histological sections of the femoral arteries also showed less cross-sectional area narrowing by plaque in rabbits treated with r-hirudin compared with those treated with heparin (22 +/- 16% verus 48 +/- 29%, p = 0.01). Both groups had similar numbers of arteries with histological evidence of balloon-induced plaque tear (12 of 13 versus 13 of 15). CONCLUSIONS: Rabbits receiving r-hirudin at the time of experimental balloon angioplasty had significantly less restenosis by angiography and by quantitative histopathology than rabbits receiving heparin.
I J Sarembock; S D Gertz; L W Gimple; R M Owen; E R Powers; W C Roberts
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Circulation     Volume:  84     ISSN:  0009-7322     ISO Abbreviation:  Circulation     Publication Date:  1991 Jul 
Date Detail:
Created Date:  1991-08-05     Completed Date:  1991-08-05     Revised Date:  2010-03-24    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  232-43     Citation Subset:  AIM; IM    
University of Virginia Health Sciences Center, Department of Medicine, Charlottesville 22908.
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MeSH Terms
Angioplasty, Balloon*
Arteriosclerosis / pathology,  therapy*
Femoral Artery*
Fibrinolytic Agents / pharmacology*
Hirudins / analogs & derivatives*,  pharmacology
Recombinant Proteins / pharmacology
Thrombolytic Therapy*
Reg. No./Substance:
0/Fibrinolytic Agents; 0/Hirudins; 0/Recombinant Proteins; 120993-53-5/desirudin
Comment In:
Circulation. 1992 May;85(5):1952-3; author reply 1953-4   [PMID:  1533354 ]
Circulation. 1991 Jul;84(1):432-5   [PMID:  2060116 ]

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