载Rapamycin多聚物涂层支架在猪冠状动脉模型预防再狭窄的实验研究

The study of rapamycin eluting polymer coated stents to prevent restenosis in the porcine coronary injury model

目的 评价载Rapamycin(RAP)新型可降解多聚物涂层支架在小型猪冠状动脉模型的可行性、安全性和预防再狭窄的疗效。方法 体外模拟测定从药物从膜释放的持续时间。支架多聚乳酸 /多聚羟基乙酸 (PLGA)涂层包埋RAP药物剂量为 4 0 0 μg(小剂量 )或 80 0 μg(大剂量 )。小型猪冠状动脉置入过大的裸支架、单PLGA涂层支架或含RAP涂层支架并形成冠状动脉损伤模型 ,术后第 5周重复定量冠状动脉造影术 (QCA)后处死动物 ,测定三组支架血管段的损伤积分、冠状动脉横断面积、管腔面积、内膜厚度和面积 ,并作比较。同时观察支架边缘段 5mm内血管组织。结果 药物从涂层膜释放时间达 30d。三组分别为裸支架组 (置入支架数n =5 ) ,单涂层组 (n =7)和RAP组 (n =8,其中小剂量为 3只 ,大剂量组为 5只 )。三组冠状动脉大小和血管损伤程度基本相同 ,裸支架组、单涂层组和RAP组的血管平均损伤积分分别为 1 84± 0 32 ,1 83± 0 35和 1 83± 0 2 6 (P =0 996 )。术后 5周 ,三组的管腔面积分别为 (6 7± 1 5 )mm2 ,(5 8± 4 0 )mm2 和 (9 7± 2 1)mm2 (P <0 0 5 ) ,RAP组最大。平均内膜厚度分别为 (0 5 1± 0 12 )mm ,(0 6 4± 0 46 )mm和 (0 2 0± 0 11)mm(P <0 0 5 ) ,RAP组最小。三组均未见支架边缘狭窄和?

Objectives To assess the feasibility, safety and efficacy of implanting rapamycin eluting ploymer coated stents in the porcine coronary injury model Methods The stents were coated with RAP suspended in poly lactic acid/polyglycolic acid (PLGA) The coated stents contained a fixed amount of RAP, 400μg(low dosage) or 800μg (high dosage) Bare stents( n =5), stents coated with PLGA( n =7) or stents coated with RAP in PLGA (RAP group n =8, low dosage subgroup n =3)were overexpanded in a porcine coronary artery model Quantitative coronary angiography(QCA) were peformed after 5 weeks follow up The cross section of the stented coronary arteries was analyzed for neointimal formation Results The mean injury scores were similar in three groups(1 84±0 32, 1 83±0 35 and 1 83±0 26 P =0 996) A larger luminal area and a less neointimal hyperplasia in RAP group were found, compared with those in bare stent group and sole PLGA coated stent group [luminal area (9 7±2 1)mm 2, (6 7±1 5) mm 2 and (5 8±3 9)mm 2, respectively] Neointimal thickness was (0 20±0 11)mm, (0 51±0 12)mm 2 and (0 64±0 46)mm 2 in the three groups, respectively ( P <0 05) No edge stenosis and thrombosis were observed Neointimal thickness was similar between both RAP subgroups [(0 21±0 13)mm 2, and (0 20±0 10)mm 2, P =0 99] Conclusions The implantation of RAP eluting stents was feasible and safe in porcine coronary injury model Neointimal hyperplasia after stenting was maximally eliminated in the RAP group for at least 5 week follow up