Perivenous application of cyanoacrylate tissue sealants reduces intimal and medial thickening of the vein graft and inflammatory responses in a rabbit model of carotid artery bypass grafting
Perivenous application of cyanoacrylate tissue sealants reduces intimal and medial thickening of the vein graft and inflammatory responses in a rabbit model of carotid artery bypass grafting
复制标题
DOI：
10.1093/ejcts/ezv111
复制
发表时间：
2016-02-01
影响因子：
3.4
通讯作者：
Yu, Yang
中科院分区：
文献类型：
--
作者：
Dai, Longsheng;Gao, Mingxin;Yu, Yang
预防冠状动脉旁路移植术（CABG）后静脉移植失败的有效治疗方法仍然缺乏。α-氰基丙烯酸酯（α-CA，99%正辛基-α-氰基丙烯酸酯+正丁基-α-氰基丙烯酸酯）由于其抑菌、可生物降解和止血特性，已越来越多地用作伤口闭合的组织密封剂。作为一种强的组织粘合剂，α-CA可能阻止动脉循环诱导的对静脉移植物的机械牵拉，从而减轻内膜增生。在此，我们研究了在颈动脉旁路移植术的兔模型中静脉周围应用α-CA对静脉移植物的影响。健康新西兰白色兔被随机分为无移植物、移植物和移植物+ α-CA组（n = 10/组）。用颈静脉转流兔颈动脉。在完成吻合后，将α-CA密封剂喷洒在整个颈静脉移植物上，包括两个吻合部位。术后4周观察移植静脉的血流参数和组织学特征，包括血管壁厚度、内侧弹力膜数量和增殖指数。促炎因子、趋化因子、（C-C基序）配体-2（CCL-2）和肿瘤坏死因子-α术后4周采用定量逆转录聚合酶链反应或酶联免疫吸附法检测移植静脉中肿瘤坏死因子-α（TNF-α）的含量，并与术后4周未处理的移植静脉比较，α-CA喷雾显著改善了接枝流动（39.4 +/- 1.5 vs 27.8 +/- 2.9 ml/min，P < 0.01），内膜和中膜增厚减弱（116.3 ± 1.0 vs 159.7 ± 0.9 μ m，P < 0.01），移植静脉抗增殖细胞核抗原增殖指数降低（15.0 ± 0.4vs23.6 ± 0.4%，P < 0.01），降低纤溶酶原激活物抑制剂-1和CCL-2的mRNA水平，降低血清TNF-α水平（92.9 +/- 1.7 vs 102.7 +/- 1.8 pg/ml，P < 0.01）。在颈动脉旁路移植术的兔模型中，静脉周围应用α-CA密封剂对静脉移植物发挥短期有益作用并减少炎症反应。α-CA对静脉移植物重塑的长期影响以及α-CA在CABG中的临床意义仍有待于未来的研究确定。
Effective therapies to prevent vein graft failure after coronary artery bypass grafting (CABG) are still lacking. alpha-Cyanoacrylate (alpha-CA, 99% n-octyl-alpha-cyanoacrylate + n-butyl-alpha-cyanoacrylate) has been increasingly used as a tissue sealant for wound closure because of its bacteriostatic, biodegradable and haemostatic properties. As a strong tissue adhesive, alpha-CA might prevent an arterial circulation-induced mechanical stretch on vein graft to attenuate intimal hyperplasia. Here, we investigated the effects of perivenous application of alpha-CA on the vein graft in a rabbit model of carotid artery bypass grafting.Healthy New Zealand white rabbits were randomized into no graft, graft or graft + alpha-CA group (n = 10 per group). Rabbit carotid artery was bypassed with the jugular vein. alpha-CA sealants were sprayed on the entire jugular graft including both anastomotic sites after completion of anastomoses. Blood flow parameters and histological characteristics of the vein grafts including vessel wall thickness, number of medial elastic lamina and proliferation index were evaluated 4 weeks after the surgery. The mRNA or protein levels of proinflammatory factors, chemokine (C-C motif) ligand-2 (CCL-2) and tumour necrosis factor-alpha (TNF-alpha) were measured 4 weeks after the operation by quantitative reverse transcription polymerase chain reaction or enzyme-linked immunosorbent assay.Compared with the untreated vein grafts at Week 4 after the operation, the alpha-CA spray significantly improved graft flow (39.4 +/- 1.5 vs 27.8 +/- 2.9 ml/min, P < 0.01), attenuated intimal and medial thickening (116.3 +/- 1.0 vs 159.7 +/- 0.9 mu m, P < 0.01), reduced anti-proliferating cell nuclear antigen proliferation index of the vein grafts (15.0 +/- 0.4 vs 23.6 +/- 0.4%, P < 0.01), decreased the mRNA levels of plasminogen activator inhibitor-1 and CCL-2, and reduced the serum levels of TNF-alpha (92.9 +/- 1.7 vs 102.7 +/- 1.8 pg/ml, P < 0.01).Perivenous application of alpha-CA sealants exerts short-term beneficial effects on the vein graft and reduces inflammatory responses in a rabbit model of carotid artery bypass grafting. Long-term effects of alpha-CA on vein graft remodelling and the clinical significance of alpha-CA in CABG remain to be determined in future studies.