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在兔颈动脉旁路移植模型中,氰基丙烯酸酯组织密封剂的静脉周围应用可减少静脉移植物的内膜和中膜增厚以及炎症反应。

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.

作者信息

Dai Longsheng, Gao Mingxin, Gu Chengxiong, Zhang Fan, Yu Yang

机构信息

Department of Cardiac Surgery, Beijing An Zhen Hospital, Capital Medical University, Beijing, China Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.

Department of Cardiac Surgery, Beijing An Zhen Hospital, Capital Medical University, Beijing, China.

出版信息

Eur J Cardiothorac Surg. 2016 Feb;49(2):675-81. doi: 10.1093/ejcts/ezv111. Epub 2015 Apr 2.

Abstract

OBJECTIVES

Effective therapies to prevent vein graft failure after coronary artery bypass grafting (CABG) are still lacking. α-Cyanoacrylate (α-CA, 99% n-octyl-α-cyanoacrylate + n-butyl-α-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, α-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 α-CA on the vein graft in a rabbit model of carotid artery bypass grafting.

METHODS

Healthy New Zealand white rabbits were randomized into no graft, graft or graft + α-CA group (n = 10 per group). Rabbit carotid artery was bypassed with the jugular vein. α-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-α (TNF-α) were measured 4 weeks after the operation by quantitative reverse transcription polymerase chain reaction or enzyme-linked immunosorbent assay.

RESULTS

Compared with the untreated vein grafts at Week 4 after the operation, the α-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 μm, 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-α (92.9 ± 1.7 vs 102.7 ± 1.8 pg/ml, P < 0.01).

CONCLUSION

Perivenous application of α-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 α-CA on vein graft remodelling and the clinical significance of α-CA in CABG remain to be determined in future studies.

摘要

目的

冠状动脉旁路移植术(CABG)后预防静脉移植物失败的有效疗法仍很缺乏。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)因其抑菌、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。作为一种强力组织粘合剂,α-CA可能预防动脉循环引起的静脉移植物机械拉伸,以减轻内膜增生。在此,我们在兔颈动脉旁路移植模型中研究了静脉周围应用α-CA对静脉移植物的影响。

方法

将健康的新西兰白兔随机分为无移植物组、移植物组或移植物+α-CA组(每组n = 10)。用颈静脉对兔颈动脉进行旁路移植。吻合完成后,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周评估静脉移植物的血流参数和组织学特征,包括血管壁厚度、中层弹性膜数量和增殖指数。术后4周通过定量逆转录聚合酶链反应或酶联免疫吸附测定法测量促炎因子、趋化因子(C-C基序)配体-2(CCL-2)和肿瘤坏死因子-α(TNF-α)的mRNA或蛋白水平。

结果

与术后第4周未处理的静脉移植物相比,α-CA喷洒显著改善了移植物血流(39.4±1.5 vs 27.8±2.9 ml/min,P < 0.01),减轻了内膜和中层增厚(116.3±1.0 vs 159.7±0.9μm,P < 0.01),降低了静脉移植物的抗增殖细胞核抗原增殖指数(15.0±0.4 vs 23.6±0.4%,P < 0.01),降低了纤溶酶原激活物抑制剂-1和CCL-2的mRNA水平,并降低了TNF-α的血清水平(92.9±1.7 vs 102.7±1.8 pg/ml,P < 0.01)。

结论

在兔颈动脉旁路移植模型中,静脉周围应用α-CA密封剂对静脉移植物有短期有益作用,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未来研究确定。

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