Kohler Ted R, Toleikis Philip M, Gravett David M, Avelar Rui L
Veteran Affairs Puget Sound Health Care System, University of Washington Medical School, Seattle, WA 98195-8280, USA.
J Vasc Surg. 2007 May;45(5):1029-1037; discussion 1037-8. doi: 10.1016/j.jvs.2007.01.057.
This study evaluated the effect of a bioabsorbable mesh containing paclitaxel on neointimal hyperplasia in a sheep model of dialysis access failure.
Forty neutered male sheep were randomized to one of five parallel groups: no mesh; or a 3-cm x 6-cm mesh with 0.0, 0.3, 0.7, or 1.2 microg/mm(2) of paclitaxel for a total dose of 0.0, 0.6, 1.3, or 2.2 mg, respectively. Commercially available 6-mm internal diameter expanded polytetrafluoroethylene grafts were surgically placed between the left common carotid artery and the right external jugular vein. For those animals randomized to one of the mesh groups, the mesh was placed around the distal end of the graft and venous anastomosis. Patency was assessed at weekly intervals throughout the study. Animals were euthanized 8 weeks after implantation, and grafts and veins were harvested. After histologic processing, six cross sections were cut at the venous end of the graft and vessel. The primary and secondary efficacy outcome measures, respectively, were the area and capillary density of the neointima at the graft-vein anastomosis. Histologic analyses were also performed to investigate the effects of the paclitaxel-eluting mesh on the anastomotic site.
Grafts occluded before the scheduled sacrifice in five animals, and they were excluded from the study and not replaced. Control animals developed significant neointimal hyperplasia at the cross section taken perpendicular to the graft at its most distal end: the neointimal area measured 10.5 +/- 6.8 mm(2) in the no mesh group and 6.4 +/- 3.2 mm(2) in the zero-dose mesh group (P = .28). In contrast, neointimal area was significantly reduced in the paclitaxel mesh groups: 0.9 +/- 1.4 mm(2) in the 0.3 microg/mm(2) group (P = .008 vs zero-dose mesh), 1.3 +/- 1.5 mm(2) in the 0.7 microg/mm(2) group (P = .004 vs zero-dose mesh), and 1.2 +/- 1.4 mm(2) in the 1.2 microg/mm(2) group (P = .008 vs zero-dose mesh). Capillary density in the neointima at the graft-vein anastomosis decreased with paclitaxel and was significantly reduced in the paclitaxel mesh groups with 0.3 and 1.2 mug/mm(2) compared with the zero-dose mesh control (3.6 +/- 2.9 vs 8.9 +/- 5.6 per mm(2) [P = .022] and 1.1 +/- 1.7 vs 8.9 +/- 5.6 per mm(2) [P = .001] respectively). The paclitaxel mesh had no significant effect on healing of the anastomosis or on the thickness of the adjacent vein.
In this model, the paclitaxel-eluting mesh significantly reduced neointimal hyperplasia and neointimal capillary density without apparent toxicity to the adjacent vein.
本研究评估了含紫杉醇的生物可吸收网片对透析通路失败绵羊模型新生内膜增生的影响。
40只去势雄性绵羊被随机分为五个平行组之一：不使用网片；或使用尺寸为3 cm×6 cm、紫杉醇含量分别为0.0、0.3、0.7或1.2 μg/mm²的网片，总剂量分别为0.0、0.6、1.3或2.2 mg。将市售的内径6 mm的膨体聚四氟乙烯移植物手术植入左颈总动脉和右颈外静脉之间。对于随机分为网片组之一的动物，将网片放置在移植物远端和静脉吻合口周围。在整个研究过程中每周评估通畅情况。植入8周后对动物实施安乐死，取出移植物和静脉。经过组织学处理后，在移植物和血管的静脉端切取六个横截面。主要和次要疗效指标分别是移植物-静脉吻合处新生内膜的面积和毛细血管密度。还进行了组织学分析以研究紫杉醇洗脱网片对吻合部位的影响。
五只动物的移植物在预定处死前发生堵塞，将它们排除在研究之外且未进行替换。对照动物在移植物最远端垂直方向的横截面处出现了明显的新生内膜增生：无网片组新生内膜面积为10.5±6.8 mm²，零剂量网片组为6.4±3.2 mm²（P = 0.28）。相比之下，紫杉醇网片组的新生内膜面积显著减小：0.3 μg/mm²组为0.9±1.4 mm²（与零剂量网片组相比，P = 0.008），0.7 μg/mm²组为1.3±1.5 mm²（与零剂量网片组相比，P = 0.004），1.2 μg/mm²组为1.2±1.4 mm²（与零剂量网片组相比，P = 0.008）。移植物-静脉吻合处新生内膜中的毛细血管密度随紫杉醇含量增加而降低，与零剂量网片对照组相比，0.3和1.2 μg/mm²的紫杉醇网片组显著降低（分别为3.6±2.9/mm²对8.9±5.6/mm² [P = 0.022]以及1.1±1.7/mm²对8.9±5.6/mm² [P = 0.001]）。紫杉醇网片对吻合口愈合或相邻静脉厚度没有显著影响。
在该模型中，紫杉醇洗脱网片显著减少了新生内膜增生和新生内膜毛细血管密度，且对相邻静脉无明显毒性。
