Abstract
Drug eluting stents (DES) induce delayed arterial healing in man, however, the ideal animal model for predicting the vascular response to DES placement in man is lacking. Hypercholesterolemic (1% cholesterol diet for 5 weeks followed by 0.025% for 4 weeks before stent implantation) New Zealand White rabbits (n=21) received bilateral stents implanted in iliac arteries. Animals were randomized to bare metal stent (Driver), zotarolimus- (Endeavor), sirolimus- (Cypher), and everolimus- (Xience V) eluting stents. Stents were harvested 4 weeks after stent implantation. Morphometric/pathologic analysis was performed. Macrophage infiltration was assessed by RAM-11 immunostaining. Blood cholesterol levels peaked at 5 weeks after initiation of the cholesterol diet which ranged from 1400 –2000mg/dL, followed by ideal range of 500 to 800mg/dL at 9 weeks (stent implantation), and were similar among groups. While EEL, and stent area were comparable in all groups, neointimal formation was significantly more suppressed in Xience and Cypher followed by Endeavor. All DES showed significantly less neointimal formation versus Driver by suppressing cell proliferation (reduced BrdU positive cells, in intima and media). Fibrin deposition, the prevalence of uncovered struts, and the number of adherent luminal inflammatory cells were greater in Xience and Cypher as compared to Driver and Endeavor. All DES showed significantly less macrophage infiltration as compared to BMS. An atherosclerotic rabbit model mimics neointimal formation in various DES and BMS similar to man with greater number of uncovered stent struts and luminal inflammation seen in Cypher and Xience as compared to Endeavor and Driver. Therefore, the atherosclerotic model is a more appropriate model for the assessment of DES efficacy as well as safety. Morphometric Analysis
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