Walpoth Beat H, Zammaretti Prisca, Cikirikcioglu Mustafa, Khabiri Ebrahim, Djebaili M Karim, Pache Jean-Claude, Tille Jean-Christophe, Aggoun Yacine, Morel Denis, Kalangos Afksendiyos, Hubbell Jeffrey A, Zisch Andreas H
Clinic of Cardiovascular Surgery, University of Geneva, Switzerland.
J Thorac Cardiovasc Surg. 2007 May;133(5):1163-70. doi: 10.1016/j.jtcvs.2007.01.029.
Intimal hyperplasia and surface thrombogenicity are major factors in the high failure rate of synthetic small-diameter bypass grafts. Vascular endothelial growth factor is a potent stimulus for endothelial growth, and its provision in a fibrin matrix coating at the luminal graft surface may hold a key to spontaneous graft endothelialization and improved graft patency.
Pigs underwent bilateral carotid artery interposition of expanded polytetrafluoroethylene grafts either impregnated with fibrin (n = 11)--engineered to locally release vascular endothelial growth factor121 (vascular endothelial growth factor-fibrin; n = 11)--or left uncoated (n = 12). Graft patency was assessed by quantitative carotid angiography followed by graft histomorphometry at the 1-month experimental end point.
Patency rates were not significantly different between study groups. Grafts coated with fibrin or vascular endothelial growth factor-fibrin exhibited significantly increased angiographic narrowing at the proximal anastomosis (for both P < .05 vs uncoated) and no difference at the distal anastomosis and the grafts' middle. Histological analysis showed 80% to 90% endothelial coverage and buildup of intima throughout the lengths of all grafts. Examination of the grafts' midportion revealed significantly enlarged neointimal layers of smooth muscle actin-positive cells in grafts coated with vascular endothelial growth factor-fibrin (242 +/- 47 microm2/micron) and fibrin (177 +/- 41 microm2/micron), compared with uncoated grafts (131 +/- 39 microm2/micron) (for both P < .05 vs uncoated). This thickening could not be explained by enhanced inflammation or vessel wall angiogenesis, which were minimal at the experimental end point.
Fibrin and vascular endothelial growth factor produced effects deleterious to graft healing, by increasing the narrowing at proximal anastomosis and neointimal growth beyond that seen in uncoated grafts. It may reflect direct activation by exogenous vascular endothelial growth factor of vascular smooth muscle cells.
内膜增生和表面血栓形成是合成小口径旁路移植物高失败率的主要因素。血管内皮生长因子是内皮生长的有力刺激因素，在移植物管腔表面的纤维蛋白基质涂层中提供该因子可能是移植物自发内皮化和改善移植物通畅性的关键。
对猪进行双侧颈动脉置换，植入膨体聚四氟乙烯移植物，其中11个移植物浸渍有纤维蛋白（设计为局部释放血管内皮生长因子121，即血管内皮生长因子 - 纤维蛋白组，n = 11），12个移植物未涂层（对照组，n = 12）。在1个月的实验终点，通过定量颈动脉血管造影评估移植物通畅性，随后进行移植物组织形态学测量。
各研究组之间的通畅率无显著差异。涂有纤维蛋白或血管内皮生长因子 - 纤维蛋白的移植物在近端吻合处血管造影显示狭窄显著增加（两者与未涂层相比P < 0.05），在远端吻合处和移植物中部无差异。组织学分析显示所有移植物全长的内皮覆盖率为80%至90%，内膜增厚。检查移植物中部发现，与未涂层移植物（131 +/- 39μm²/μm）相比，涂有血管内皮生长因子 - 纤维蛋白（242 +/- 47μm²/μm）和纤维蛋白（177 +/- 41μm²/μm）的移植物中平滑肌肌动蛋白阳性细胞的新生内膜层显著增大（两者与未涂层相比P < 0.05）。这种增厚不能用炎症增强或血管壁血管生成来解释，在实验终点时炎症和血管生成均很轻微。
纤维蛋白和血管内皮生长因子对移植物愈合产生有害影响，表现为近端吻合处狭窄增加以及新生内膜生长超过未涂层移植物，这可能反映了外源性血管内皮生长因子对血管平滑肌细胞的直接激活作用。
