Neointimal thickening after stent delivery of paclitaxel: Change in composition and arrest of growth over six months
Neointimal thickening after stent delivery of paclitaxel: Change in composition and arrest of growth over six months
复制标题
DOI：
10.1016/s0735-1097(00)01020-2
复制
发表时间：
2000-12-01
影响因子：
24
通讯作者：
Rogers, C
中科院分区：
文献类型：
--
作者：
Drachman, DE;Edelman, ER;Rogers, C
目的：本研究的目的是确定基于支架的紫杉醇输送对支架植入术后内膜增厚的数量、速率和组成的长期影响。紫杉醇在体外和体内均能抑制血管平滑肌细胞的增殖和迁移。这些作用，加上低溶解度，使其成为局部给药后调节血管损伤反应和延长效果的可行候选者。我们询问在支架涂有生物可降解聚合物的支架上局部递送紫杉醇几周是否可以在支架植入后6个月内持续减少内膜增生。方法采用不锈钢支架在兔髂动脉内皮剥脱后植入。支架未包被或包被薄层聚（乳酸-co- sigma -己内酯）共聚物单独或含有紫杉醇，200马克杯。紫杉醇体外释放遵循一级动力学2个月。分别于植入后7、28、56或180天检测组织反应。结果紫杉醇在支架植入术后7天将内膜和内侧细胞增殖降低了3倍，几乎消除了后期内膜增厚。植入后6个月，药物释放和聚合物降解很可能完成后，紫杉醇释放支架的内膜面积降低了2倍。紫杉醇处理后血管的组织反应包括不完全愈合，少量平滑肌细胞，巨噬细胞的后期存留和密集的纤维蛋白伴少量胶原。结论：聚（丙交酯-co- sigma -己内酯）共聚物包被支架允许持续的紫杉醇递送，在支架植入后数月，在可能完成药物递送和聚合物降解后很长一段时间内，几乎可以消除新生内膜增生。(C) 2000年由美国心脏病学会发布。
OBJECTIVES The purpose of this study was to determine long-term effects of stent-based paclitaxel delivery on amount, rate and composition of neointimal thickening after stent implantation.BACKGROUND Paclitaxel prevents vascular smooth muscle cell proliferation and migration in vitro and in vivo. These actions, coupled with low solubility, make it a viable candidate for modulating vascular responses to injury and prolonged effects after local delivery. We asked whether local delivery of paclitaxel for a period of weeks from a stent coated with a bioerodible polymer could produce a sustained reduction in neointimal hyperplasia for up to six months after stenting.METHODS Stainless steel stents were implanted in the iliac arteries of rabbits after endothelial denudation. Stents were uncoated or coated with a thin layer of poly(lactide-co-Sigma -caprolactone) copolymer alone or containing paclitaxel, 200 mug. Paclitaxel release in vitro followed first-order kinetics for two months. Tissue responses were examined 7, 28, 56 or 180 days after implantation.RESULTS Paclitaxel reduced intimal and medial cell proliferation three-fold seven days after stenting and virtually eliminated later intimal thickening. Six months after stenting, long after drug release and polymer degradation were likely complete, neointimal area was two-fold lower in paclitaxel-releasing stents. Tissue responses in paclitaxel treated vessels included incomplete healing, few smooth muscle cells, late persistence of macrophages and dense fibrin with little collagen.CONCLUSIONS Poly(lactide-co-Sigma -caprolactone) copolymer-coated stents permit sustained paclitaxel delivery in a manner that virtually abolishes neointimal hyperplasia for months after stent implantation, long after likely completion of drug delivery and polymer degradation. (C) 2000 by the American College of Cardiology.