Combining sirolimus-eluting stents and external irradiation in cholesterol-fed rabbits increased incomplete stent apposition and decreased re-endothelialization.
Restenosis after the implantation of a drug-eluting stent or after vascular irradiation therapy shares similar physiopathological mechanisms. No experimental data are currently available on vascular wall behavior after external irradiation on arteries stented with sirolimus-eluting stents (SES). Ten New Zealand white rabbits received a 0.5% cholesterol-enriched chow for 1 month. Bilateral iliac artery stent implantation was then performed with an SES (Cypher; Cordis Corp). The animals were randomized into either an irradiated group (I, 2 Gy external x-ray irradiation, n = 5) or a control group (C, n = 5). The cholesterol-enriched chow was continued for 1 additional month after stent implantation. The stented arteries were harvested for histological analyses. The number and the percentage of incompletely apposed stents struts (IASS) were significantly higher in irradiated versus control group (3.05 +/- 0.46 vs. 1.57 +/- 0.27 IASS, P < 0.01, and 28.44% +/- 3.97% vs. 15.2% +/- 2.46% of IASS, P < 0.01, respectively). The mean neointimal thickness behind the IASS was also higher in the irradiated group (I: 28.3 +/- 2.5 microm vs. C: 18.2 +/- 2.3 microm, P < 0.01). Re-endothelialization was lower in irradiated group (I: 44.6% +/- 17.5% vs. C: 75.2% +/- 5.7%, P < 0.01). The present study revealed that low-dose external irradiation increased incomplete stent apposition and reduced re-endothelialization of SES. These results underscore the potential deleterious cumulative side effects of these 2 procedures to prevent restenosis.
Busseuil
David
D
Laboratory of Cardiovascular and Experimental Physiopathology and Pharmacology, Faculties of Medicine and Pharmacy, University of Burgundy, Dijon, France.
Collin
Bertrand
B
Rioufol
Gilles
G
Korandji
Claudia
C
Zeller
Marianne
M
Maingon
Philippe
P
Briot
François
F
Cottin
Yves
Y
Rochette
Luc
L
D000818:Animals; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D004307:Dose-Response Relationship, Radiation; D054855:Drug-Eluting Stents / Q000009:adverse effects*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000528:radiation effects* / Q000648:ultrastructure; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D011817:Rabbits; D020123:Sirolimus / Q000494:pharmacology*; D013997:Time Factors; D017539:Tunica Intima / Q000528:radiation effects; D017540:Tunica Media / Q000528:radiation effects; D014965:X-Rays
D002791:Cholesterol, Dietary; D007166:Immunosuppressive Agents; D002784:Cholesterol; D020123:Sirolimus