Abbott Laboratories, Abbott Park, IL 60064-6215, USA.
J Vasc Surg. 2012 Dec;56(6):1680-8. doi: 10.1016/j.jvs.2012.04.022. Epub 2012 Jul 27.
A novel self-expanding, drug-eluting stent (DES) was designed to slowly release everolimus in order to prevent restenosis after percutaneous peripheral intervention. The purpose of this experimental animal study was to test the hypothesis that long-term local, stent-mediated delivery of everolimus would reduce neointimal hyperplasia in porcine iliac arteries.
The iliac arteries of 24 Yucatan mini-swine were percutaneously treated with overlapping 8- × 28-mm self-expanding nitinol stents loaded with everolimus (225 μg/cm2 stent surface area) formulated in a poly(ethylene-co-vinyl alcohol) copolymer intended to deliver the drug in a sustained fashion over about 6 months (DES). Bare nitinol self-expanding stents (bare metal stent [BMS]) were implanted in an identical fashion on the contralateral side to serve as controls. After 3, 6, or 12 months, the animals were sacrificed and the stented arteries perfusion-fixed for histomorphometric analysis.
The chronic presence of everolimus in arterial tissue reduced stent-induced inflammation after 3 months (inflammation score: BMS 2.29±0.44 vs DES 0.17±0.17; P=.001) and 6 months (BMS 2.06±0.43 vs DES 0.50±0.5; P=.007), although some late inflammation was observed after drug exhaustion (BMS 1.00±0.25 vs DES 2.56±0.62 after 12 months; P=not significant [NS]). Treatment with locally delivered everolimus significantly reduced neointimal hyperplasia after 3 months (neointimal thickness: BMS 0.79±0.20 vs DES 0.37±0.04 mm; P=.03) and 6 months (BMS 0.73±0.14 vs DES 0.41±0.08 mm; P=.05), although the effect had dissipated after 12 months (BMS 0.68±0.11 vs DES 0.67±0.11 mm; P=NS). Remarkably, stent-induced neoatherosclerosis, characterized by the histologic presence of foamy macrophages and cholesterol clefts, was significantly attenuated by treatment with everolimus (atherogenic change scores at 3 months: BMS 0.56±0.15 vs DES 0.04±0.04; P=.003; 6 months: BMS 0.84±0.23 vs DES 0.00±0.00; P=.004; and 12 months: BMS 0.09±0.10 vs DES 0.19±0.19; P=NS).
In this experimental animal model, local arterial stent-mediated delivery of everolimus inhibited the formation of neointimal hyperplasia and neoatherosclerosis during the first 6 months. The effect was transient, however, as arterial morphology and histology appeared similar to control stented arteries after 12 months.
一种新型的自扩张、载药支架（DES）被设计用于缓慢释放依维莫司，以防止经皮外周介入治疗后的再狭窄。本实验动物研究的目的是验证以下假设：在猪髂动脉中，长期局部、支架介导的依维莫司递送可减少新生内膜增生。
24 只 Yucatan 小型猪的髂动脉通过重叠 8×28mm 的自扩张镍钛合金支架进行经皮治疗，支架表面涂有依维莫司（225μg/cm2），药物由聚乙烯醇共聚物配方制成，旨在 6 个月内持续释放药物（DES）。在对侧植入相同设计的裸镍钛合金自扩张支架（裸金属支架[BMS]）作为对照。3、6 或 12 个月后，处死动物并对支架血管进行灌注固定以进行组织形态计量学分析。
动脉组织中依维莫司的慢性存在减少了 3 个月（炎症评分：BMS 2.29±0.44 与 DES 0.17±0.17；P=.001）和 6 个月（BMS 2.06±0.43 与 DES 0.50±0.5；P=.007）时支架引起的炎症，但在药物耗尽后观察到一些晚期炎症（BMS 1.00±0.25 与 DES 2.56±0.62 后 12 个月；P=无显著意义[NS]）。局部给予依维莫司可显著减少 3 个月（新生内膜厚度：BMS 0.79±0.20 与 DES 0.37±0.04mm；P=.03）和 6 个月（BMS 0.73±0.14 与 DES 0.41±0.08mm；P=.05）时的新生内膜增生，但 12 个月后效果消失（BMS 0.68±0.11 与 DES 0.67±0.11mm；P=NS）。值得注意的是，依维莫司治疗显著减轻了支架诱导的新生动脉粥样硬化，其特征为泡沫巨噬细胞和胆固醇裂隙的组织学存在（3 个月时动脉粥样硬化变化评分：BMS 0.56±0.15 与 DES 0.04±0.04；P=.003；6 个月：BMS 0.84±0.23 与 DES 0.00±0.00；P=.004；12 个月：BMS 0.09±0.10 与 DES 0.19±0.19；P=NS）。
在这个实验动物模型中，局部动脉支架介导的依维莫司递送在最初的 6 个月内抑制了新生内膜增生和新生动脉粥样硬化的形成。然而，这种效果是短暂的，因为 12 个月后动脉形态和组织学与对照支架血管相似。
