title: Combining sirolimus-eluting stents and external irradiation in cholesterol-fed rabbits increased incomplete stent apposition and decreased re-endothelialization.
abstract: 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.
authors.affiliation: Laboratory of Cardiovascular and Experimental Physiopathology and Pharmacology, Faculties of Medicine and Pharmacy, University of Burgundy, Dijon, France.
authors.forename: David
authors.initials: D
authors.lastname: Busseuil
authors.forename: Bertrand
authors.initials: B
authors.lastname: Collin
authors.forename: Gilles
authors.initials: G
authors.lastname: Rioufol
authors.forename: Claudia
authors.initials: C
authors.lastname: Korandji
authors.forename: Marianne
authors.initials: M
authors.lastname: Zeller
authors.forename: Philippe
authors.initials: P
authors.lastname: Maingon
authors.forename: François
authors.initials: F
authors.lastname: Briot
authors.forename: Yves
authors.initials: Y
authors.lastname: Cottin
authors.forename: Luc
authors.initials: L
authors.lastname: Rochette
mesh_terms: 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
chemical_list: D002791:Cholesterol, Dietary; D007166:Immunosuppressive Agents; D002784:Cholesterol; D020123:Sirolimus