Rapamycin-coated expanded polytetrafluoroethylene bypass grafts exhibit decreased anastomotic neointimal hyperplasia in a porcine model
Rapamycin-coated expanded polytetrafluoroethylene bypass grafts exhibit decreased anastomotic neointimal hyperplasia in a porcine model
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DOI：
10.1016/j.jvs.2005.06.018
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发表时间：
2005-11-01
影响因子：
4.3
通讯作者：
Fabian, TC
中科院分区：
文献类型：
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作者：
Cagiannos, C;Abul-Khoudoud, OR;Fabian, TC
目的：我们验证了一种假说，即雷帕霉素(雷帕霉素)包被在扩张的聚四氟乙烯(EPTFE)移植物上，并从ePTFE移植物中洗脱出来，可以抑制猪模型的新生内膜增生。方法：将雷帕霉素(又称西罗莫司)涂覆在6 mm内径的ePTFE薄壁移植物的管腔表面，使药物能够定时释放。一种可以从ePTFE中定时释放雷帕霉素的粘合聚合物是用商业上可获得的化学品开发的，并应用于6 mm的ePTFE移植物上。移植物的完整性通过扫描电子显微镜进行表征，雷帕霉素水平通过高效液相色谱进行定量。22头杂种猪随机分为3组：未处理组(n=6)、粘附组(n=6)、粘附组(n=6)和粘合剂+雷帕霉素涂层组(n=10)。采用内径6 mm的ePTFE移植物和标准化的吻合口长度，行单侧腹主动脉-髂动脉搭桥术。用聚丙烯缝线植入单侧端侧主动脉-髂骨ePTFE移植物(内径6 mm)，近端6-0个，远端7-0个，所有吻合口长12 mm。所有动物每天服用阿司匹林(325毫克口服)。从手术前一天开始，所有动物每天口服阿司匹林(325毫克)。28天后处死动物，移植物与邻近的主动脉袖带和髂动脉流出段连续移植。组间比较的变量包括移植物通畅率、远端吻合口长度和横断面狭窄，以及动脉-移植物交界处的内膜厚度与相邻移植物厚度的指数。石蜡切片进行苏木精-伊红染色和Masson三色染色。一位病理学家对实验组的切片进行盲法分级，以观察胶原沉积、新生内膜形成、炎性细胞浸润、中层坏死和动脉瘤样变性。结果：所有动物都存活了下来，直到它们被处死，没有肢体缺血或移植物感染的临床证据。单因素方差分析中的预先计划t检验显示，未治疗的ePTFE组和仅涂有粘合剂的ePTFE组之间的结果指标没有差异；因此，将它们结合起来进一步与粘合剂和雷帕霉素涂层的ePTFE组进行比较。雷帕霉素洗脱膨化聚四氟乙烯组吻合口长度较长(85.6%比60.6%)，P
Objective: We tested the hypothesis that rapamycin coated onto, and eluted from, expanded polytetrafluoroethylene (ePTFE) grafts would diminish neointimal hyperplasia in a porcine model.Methods: Rapamycin (also called sirolimus) was coated onto the luminal surface of 6-mm-internal-diameter thin-walled ePTFE grafts by using an adhesive polymer that allows timed release of the drug. An adhesive polymer that allows timed release of rapamycin from ePTFE was developed with commercially available chemicals and applied on 6-mm ePTFE grafts. Graft integrity was characterized by scanning electron microscopy, and rapamycin levels were quantified by using high-performance liquid chromatography. Twenty-two mongrel pigs were randomized into three groups: untreated ePTFE (n = 6), adhesive-only coated ePTFE (n = 6), or adhesive- and rapamycin-coated ePTFE (n = 10). End-to-side unilateral aortoiliac bypasses were performed by using 6-mm-internal-diameter ePTFE grafts and standardized anastomotic lengths. Unilateral end-to-side aortoiliac ePTFE grafts (6-mm internal diameter) were inserted by using polypropylene sutures, 6-0 proximally and 7-0 distally; all anastomoses were 12 mm long. All animals received aspirin (325 mg orally) daily. All animals were given oral aspirin (325 mg) daily beginning on the day before surgery. At 28 days, the animals were killed, and the grafts were explanted in continuity with the adjacent aortic cuff and the outflow iliac artery. Variables compared between groups included graft patency, distal anastomotic length and cross-sectional narrowing, and intimal thickness at the arterial-graft junction indexed to the adjacent graft thickness. Microscopic analysis was performed with hematoxylin and eosin and Masson trichrome stains on paraffin sections. A pathologist blinded to experimental groups graded sections for collagen deposition, neointima formation, inflammatory cellular infiltrates, medial necrosis, and aneurysmal degeneration.Results: All animals survived until they were killed without clinical evidence of limb ischemia or graft infection. Preplanned t tests in the context of one-way analysis of variance showed no difference in outcome measures between the untreated ePTFE and adhesive-only coated ePTFE groups; therefore, they were combined in further comparisons with the adhesive- and rapamycin-coated ePTFE group. The Rapamycine eluting expanded polytetrafluoroethylene group had longer anastomoses (85.6% vs 60.6% of the initial anastomotic length maintained; P