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


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 degrees 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 degrees 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 degrees 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.


CONCLUSIONS
Moderate heating represents a promising approach to prevent in-stent restenosis via the limitation of the proliferative response without thrombosis induction.
Brasselet
Camille
C
Faculté de médecine, Université Paris-Descartes, INSERM U 849, Paris, France. camille.brasselet@wanadoo.fr
Durand
Eric
E
Addad
Faouzi
F
Vitry
Fabien
F
Chatellier
Gilles
G
Demerens
Corinne
C
Lemitre
Mathilde
M
Garnotel
Roselyne
R
Urbain
Dominique
D
Bruneval
Patrick
P
Lafont
Antoine
A
D000800:Angioplasty, Balloon; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D050197:Atherosclerosis / Q000628:therapy*; D049109:Cell Proliferation; D003251:Constriction, Pathologic / Q000517:prevention & control; D004195:Disease Models, Animal; D006083:Graft Occlusion, Vascular / Q000517:prevention & control*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006358:Hot Temperature / Q000627:therapeutic use*; D006965:Hyperplasia / Q000517:prevention & control; D007083:Iliac Artery / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D011817:Rabbits; D011897:Random Allocation; D055502:Secondary Prevention; D015607:Stents; D016896:Treatment Outcome; D017539:Tunica Intima / Q000473:pathology*
D018840:HSP70 Heat-Shock Proteins