Huang Y, Salu K, Liu X, Li S, Wang L, Verbeken E, Bosmans J, De Scheerder I
Department of Cardiology, Department of Pathology, University Hospitals, Leuven, Belgium.
Heart. 2004 Feb;90(2):195-9. doi: 10.1136/hrt.2002.008169.
To evaluate the effect of stent based methotrexate delivery on neointimal hyperplasia.
Stainless steel coronary stents and biological polymer coated (SAE) stents were randomly implanted in coronary arteries of pigs with a stent to artery ratio of 1.1:1. The pigs were killed after five days (10 stents) or four weeks (20 stents). Second, stainless steel coronary stents were dip coated in a 10 mg/ml methotrexate-SAE polymer solution, resulting in a total load of 150 microg methotrexate/stent. SAE coated stents and methotrexate loaded stents were randomly implanted in porcine coronary arteries with a stent to artery ratio of 1.2:1 and followed up to four weeks.
SAE coated stents and bare stents elicited a similar tissue response at five days. At four weeks, neointimal hyperplasia induced by the coated stents was less pronounced than with the bare stents (1.32 (0.66) v 1.73 (0.93) mm2, p > 0.05). In vitro drug release studies showed that 50% of the methotrexate was released in 24 hours, and all drug was released within four weeks. No impact on vascular smooth muscle cell proliferation or viability was observed in in vitro cell cultures. At four weeks the arteries with methotrexate loaded stents had decreased peristrut inflammation and neointimal hyperplasia (1.22 (0.34) v 2.25 (1.28) mm2, p < 0.01).
SAE coating had an excellent biocompatibility with vascular tissue. Stent based delivery of methotrexate in the SAE coating effectively reduced neointimal hyperplasia in a porcine coronary stent model, potentially due to reduced peristrut inflammation.
评估基于支架的甲氨蝶呤递送对新生内膜增生的影响。
将不锈钢冠状动脉支架和生物聚合物涂层（SAE）支架以1.1:1的支架与动脉比例随机植入猪的冠状动脉。在五天后（10个支架）或四周后（20个支架）处死猪。其次，将不锈钢冠状动脉支架浸入10mg/ml甲氨蝶呤-SAE聚合物溶液中进行浸涂，使每个支架的甲氨蝶呤总负载量为150μg。将SAE涂层支架和载有甲氨蝶呤的支架以1.2:1的支架与动脉比例随机植入猪冠状动脉，并随访四周。
SAE涂层支架和裸支架在五天时引起相似的组织反应。在四周时，涂层支架诱导的新生内膜增生比裸支架轻（1.32（0.66）对1.73（0.93）mm2，p>0.05）。体外药物释放研究表明，50%的甲氨蝶呤在24小时内释放，所有药物在四周内释放。在体外细胞培养中未观察到对血管平滑肌细胞增殖或活力的影响。在四周时，载有甲氨蝶呤支架的动脉的支架周围炎症和新生内膜增生减少（1.22（0.34）对2.25（1.28）mm2，p<0.01）。
SAE涂层与血管组织具有良好的生物相容性。在SAE涂层中基于支架递送甲氨蝶呤可有效减少猪冠状动脉支架模型中的新生内膜增生，可能是由于支架周围炎症减轻。
