This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gimple, L. W. Articles by Sarembock, I. J. Search for Related Content PubMed PubMed Citation Articles by Gimple, L. W. Articles by Sarembock, I. J. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Angioplasty Cholesterol Hazardous Substances DB HEPARIN

Circulation, Vol 86, 1536-1546, Copyright © 1992 by American Heart Association

ARTICLES

Effect of chronic subcutaneous or intramural administration of heparin on femoral artery restenosis after balloon angioplasty in hypercholesterolemic rabbits. A quantitative angiographic and histopathological study

LW Gimple, SD Gertz, HL Haber, M Ragosta, ER Powers, WC Roberts and IJ Sarembock
Division of Cardiology, University of Virginia Health Sciences Center, Charlottesville 22908.

BACKGROUND. Heparin is known to have antithrombotic, anticoagulant, and antiproliferative effects. We hypothesized that chronic subcutaneous and/or direct intramural administration of heparin would reduce restenosis and inhibit plaque growth after balloon angioplasty. METHODS AND RESULTS. Focal atherosclerosis was induced bilaterally in the femoral arteries of 59 rabbits by air desiccation intimal injury and a 2% cholesterol diet. After angioplasty, the rabbits were assigned to one of four treatment groups. Control arteries (n = 21) received no additional heparin. A second group of 20 arteries was treated with a porous balloon that delivered heparin (1,500 units) directly into the arterial wall. A third group (n = 29) received subcutaneous heparin (350 units.kg-1.day-1) for 28 days, and a fourth group (n = 23) was treated with subcutaneous and intramural heparin. Quantitative angiography showed a modest reduction in restenosis (defined as the change in minimal luminal diameter from immediately after angioplasty to 28 days) with subcutaneous heparin compared with control arteries (0.32 +/- 0.18 versus 0.58 +/- 0.34 mm, p < 0.01); however, luminal diameter was not improved at 28 days compared with before angioplasty. Intramural delivery of heparin by the porous balloon catheter was confirmed by use of fluoresceinated heparin in one animal. Angiographic restenosis was not reduced in arteries treated with intramural heparin versus controls (0.61 +/- 0.54 versus 0.58 +/- 0.34 mm, p = NS). Blinded planimetric analysis of histological sections showed no differences in luminal cross-sectional area narrowing by atherosclerotic plaque, in plaque area, or in plaque/media ratio at 28 days among the four treatment groups. CONCLUSIONS. Chronic subcutaneous heparin after balloon angioplasty results in a modest reduction in angiographic restenosis in this model; however, the absolute luminal diameter is not improved compared with before angioplasty, and plaque area and percent luminal narrowing by plaque were not different among the four treatment groups. Heparin can be delivered into an atherosclerotic plaque by a porous balloon, but this treatment does not reduce restenosis after angioplasty in this model.

This article has been cited by other articles:

				E. Jeanpierre, T. Le Tourneau, I. Six, C. Zawadzki;, E. Van Belle, M. D. Ezekowitz, R. Bordet, S. Susen, B. Jude, and D. Corseaux Dietary Lipid Lowering Modifies Plaque Phenotype in Rabbit Atheroma After Angioplasty: A Potential Role of Tissue Factor Circulation, October 7, 2003; 108(14): 1740 - 1745. [Abstract] [Full Text] [PDF]

				J.-F. Deux, A. Meddahi-Pelle, A. F. Le Blanche, L. J. Feldman, S. Colliec-Jouault, F. Bree, F. Boudghene, J.-B. Michel, and D. Letourneur Low Molecular Weight Fucoidan Prevents Neointimal Hyperplasia in Rabbit Iliac Artery In-Stent Restenosis Model Arterioscler. Thromb. Vasc. Biol., October 1, 2002; 22(10): 1604 - 1609. [Abstract] [Full Text] [PDF]

				I. Ogawa, T. Hayashi, T. Nakabayashi, N. Otani, K. Ishikawa, and K. Kanamasa Prevention of Coronary Arterial Renarrowing by Continuous 3-Day Infusion of Tissue Plasminogen Activator After Successful Percutaneous Transluminal Coronary Angioplasty: A Randomized, Double-Blind, Placebo-Controlled Study Angiology, May 1, 2000; 51(5): 367 - 375. [Abstract] [PDF]

				M. A. Lovich and E. R. Edelman Tissue concentration of heparin, not administered dose, correlates with the biological response of injured arteries in vivo PNAS, September 28, 1999; 96(20): 11111 - 11116. [Abstract] [Full Text] [PDF]

				A. Lafont and D. Faxon Why do animal models of post-angioplasty restenosis sometimes poorly predict the outcome of clinical trials? Cardiovasc Res, July 1, 1998; 39(1): 50 - 59. [Full Text] [PDF]

				L. Capron, J. Jarnet, D. Heudes, D. Joseph-Monrose, and P. Bruneval Repeated Balloon Injury of Rat Aorta : A Model of Neointima With Attenuated Inhibition by Heparin Arterioscler. Thromb. Vasc. Biol., September 1, 1997; 17(9): 1649 - 1656. [Abstract] [Full Text]

				M. Ragosta, W. L. Barry, L. W. Gimple, S. D. Gertz, K. W. McCoy, G. A. Stouffer, C. A. McNamara, E. R. Powers, G. K. Owens, and I. J. Sarembock Effect of Thrombin Inhibition With Desulfatohirudin on Early Kinetics of Cellular Proliferation After Balloon Angioplasty in Atherosclerotic Rabbits Circulation, March 15, 1996; 93(6): 1194 - 1200. [Abstract] [Full Text]

				C. M. Speidel, P. R. Eisenberg, W. Ruf, T. S. Edgington, and D. R. Abendschein Tissue Factor Mediates Prolonged Procoagulant Activity on the Luminal Surface of Balloon-Injured Aortas in Rabbits Circulation, December 1, 1995; 92(11): 3323 - 3330. [Abstract] [Full Text]

				E. L. Chaikof, R. Caban, C.-N. Yan, G. N. Rao, and M. S. Runge Growth-related Responses in Arterial Smooth Muscle Cells Are Arrested by Thrombin Receptor Antisense Sequences J. Biol. Chem., March 31, 1995; 270(13): 7431 - 7436. [Abstract] [Full Text] [PDF]