Evaluation of Polymer-Based Comparator Drug-Eluting Stents Using a Rabbit Model of Iliac Artery Atherosclerosis

Abstract

Background— Although atherosclerotic models, especially in the rabbit, have existed for a long time, a comparative study of various drug-eluting stent (DES) implantations in atherosclerotic arteries have not been systematically studied. Methods and Results— New Zealand White rabbits (n=44) with induced atheroma received bilateral iliac artery stents: bare metal stent (BMS) (Driver) or a stent eluting zotarolimus (ZES) (Endeavor), sirolimus (SES) (Cypher), or everolimus (EES) (Xience V). After 28 days, tissues were harvested for histomorphometric analyses, en face analysis of endothelial coverage, and expression of endothelial nitric oxide synthase (eNOS). Area measurements of external elastic lamina and stent area were similar. Neointimal area was significantly less in all DES versus BMS, which was least in SES and EES; similar trends were noted for cell proliferation. Uncovered struts were greater for SES and EES and least in BMS, whereas ZES were in between and associated with the least fibrin. Macrophages of the neointima were significantly less for all DES relative to BMS. Plaque calcification underneath stents, however, was significantly greater in SES and ZES than in BMS. Although endothelial coverage in between struts was comparable between BMS and DES, there was significantly greater expression of eNOS in BMS and ZES relative to EES and SES. Conclusions— The rabbit atherosclerotic model of stenting showed delayed healing and significantly greater reduction of neointima following implantation of SES and EES; however, delayed healing was less in ZES with greater neointima (but less than BMS), endothelial regrowth, and eNOS expression.