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European Heart Journal Advance Access originally published online on January 22, 2008
European Heart Journal 2008 29(3):402-412; doi:10.1093/eurheartj/ehm596
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2008 The Author(s). Published by Oxford University Press on behalf of the European Society of Cardiology
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that the original authorship is properly and fully attributed; the Journal, Learned Society and Oxford University Press are attributed as the original place of publication with correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions©oxfordjournals.org

Effect of local heating on restenosis and in-stent neointimal hyperplasia in the atherosclerotic rabbit model: a dose-ranging study

Camille Brasselet1,2,*, Eric Durand1, Faouzi Addad1, Fabien Vitry3, Gilles Chatellier1, Corinne Demerens1, Mathilde Lemitre1, Roselyne Garnotel4, Dominique Urbain1, Patrick Bruneval5 and Antoine Lafont1

1 Faculté de médecine, Université Paris-Descartes, INSERM U 849, Paris, France
2 Service de cardiologie, CHU Robert Debré, Reims, France
3 Unité d'aide méthodologique, hôpital Maison Blanche, Reims, France
4 Laboratoire de Biochimie, American Memorial Hospital, Reims, France
5 INSERM U 625, Physiologie et pharmacologie vasculaire et rénale, rue de l'école de Médecine, Paris, France

Received 18 October 2006; revised 12 October 2007; accepted 13 November 2007; online publish-ahead-of-print 22 January 2008.

* Corresponding author. service de cardiologie, CHU Robert Debré, Reims, France. Tel: +33 3 26 78 70 20, Fax: +33 3 26 78 41 32. Email: camille.brasselet{at}wanadoo.fr

Aims: In-stent restenosis is related to neointimal hyperplasia. Heating reduces neointimal hyperplasia but promotes constrictive remodeling after balloon angioplasty. We aimed to assess the ability of local heating in inhibiting restenosis and in-stent neointimal hyperplasia and its potential side effects on arterial thrombosis.

Methods and results: Atherosclerotic-like lesions were induced in iliac rabbit arteries. One month later, both iliac rabbit arteries were stented. In each animal, one artery was randomized to local heating at four temperatures (50, 60, 80, and 100°C). The contra lateral artery was used as control. Angiographic and histomorphometric analysis were performed 42 days after angioplasty. Immunohistochemistry was performed 3, 15, and 42 days after angioplasty. Angiographic significant reduction of in-stent restenosis after moderate heating (50°C) was related to in-stent neointimal hyperplasia trend to be lower after moderate local heating when compared with controls. In contrast, in-stent thrombosis was similar to controls. Higher temperatures (i.e. 80 and 100°C) also reduced in-stent neointimal hyperplasia but were most frequently associated with severe in-stent thrombosis. Local heating was associated with decreased cell proliferation, collagen density, and increased smooth muscle cell apoptosis and heat shock protein expression.

Conclusion: Moderate heating represents a promising approach to prevent in-stent restenosis via the limitation of the proliferative response without thrombosis induction.

Key Words: Angioplasty • Thrombosis • Heat-shock proteins • Restenosis • Stents


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