Pre-treatment of donor with 1-deamino-8-D-arginine vasopressin could alleviate early failure of porcine xenograft in a cobra venom factor treated canine recipient
Pre-treatment of donor with 1-deamino-8-D-arginine vasopressin could alleviate early failure of porcine xenograft in a cobra venom factor treated canine recipient
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DOI：
10.1016/j.ejcts.2005.02.042
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发表时间：
2005-07-01
影响因子：
3.4
通讯作者：
Kim, YT
中科院分区：
文献类型：
--
作者：
Kang, HJ;Lee, G;Kim, YT
目的：与心脏或肾脏异种移植不同，使用眼镜蛇毒因子(CVF)耗尽补体并不能改善异种肺移植的存活率。一些病例表明，猪von Willebrand因子(VWF)可能在异种肺移植功能障碍的不同于其他器官的发病机制中发挥重要作用。为探讨vWF和补体系统在异种肺移植超急性血管损伤中的作用及机制，我们在1-去氨基-8-D-精氨酸加压素(DDAVP)和CVF预处理后，进行了猪-犬正交异性单肺移植。方法：建立3组异种肺移植模型：I组为对照组，11组为CVF组，111组为DDAVP组(9 mg/kg，3d)/受体组为CVF组(60u/kg)。移植后3h连续观察血流动力学、凝血和补体系统参数及移植肺病理变化。结果：DDAVP可降低猪肺组织中vWF的含量(7.7+/-2.4AU/mg vs 16.0+/-5.6AU/mg，P<0.0001)。移植前24小时输注CVF有效地耗尽了受者的血清C3和补体溶血活性，低于检测范围。不考虑使用CVF，移植未经修饰的移植物的I组和11组在移植后立即显示出白细胞和血小板计数下降。而在第111组，经DDAVP处理过的猪肺移植受者，移植后血小板计数未见下降(P=0.0295)。Ⅲ组血浆抗凝血酶和纤维蛋白原下降趋势减弱。光镜下可见毛细血管和较大血管内广泛的血栓形成。结论：补体抑制治疗不足以减轻异种肺移植的主要病理改变--血管内血栓形成。给供体动物预先输注DDAVP能有效地防止血小板隔离和减轻血管内血栓形成。提示以vWF为靶点的策略有望为异种肺移植的成功奠定基础。(C)2005 Elsevier B.V.保留所有权利。
Objective: Unlike cardiac or renal xenotransplants, the depletion of complement using cobra venom factor (CVF) does not improve pulmonary xenograft survival. Several cases suggest that the swine von Willebrand factor (vWF) may play a major rote in presenting a different pathogenesis of pulmonary xenograft dysfunction from other organs. To evaluate the rote of vWF and the complement system in mediating hyperacute vascular injury of pulmonary xenografts and elucidate pathogenesis of the injury, we performed swine-to-canine orthotropic single lung xenotransplantation after pre-treatment of 1-deamino-8-D-arginine vasopressin (DDAVP) and CVF. Methods: We set up three groups for lung xenotransplantation: group I served as the control group; group 11, recipients pre-treated with CVF; group 111, donors pre-treated with DDAVP (9 mg/kg, 3 days)/recipients pre-treated with CVF (60 u/kg). Hemodynamic data, coagulation and complement system parameters, and grafted lung pathologies were examined serially for 3 h after transplantation. Results: DDAVP infusion reduced the vWF content in swine lung tissue in vivo (7.7 +/- 2.4 AU/mg vs 16.0 +/- 5.6 AU/mg, P < 0.0001). Infusion of CVF 24 h prior to transplantation effectively depleted the recipient's serum C3 and complement hemolytic activity below the detectable range. Regardless of the use of CVF, both groups I and 11 transplanted with unmodified grafts showed an immediate drop in leukocytes and platelet counts after transplantation. However, in group 111, in recipients transplanted with DDAVP pre-treated swine lung, the platelet count did not decrease after transplantation (P=0.0295). The decrease of plasma antithrombin and fibrinogen tended to be attenuated in group III. Light microscopic examination revealed extensive vascular thromboses in both capillary and larger vessels, as well. as early pulmonary parenchymal damage in groups I and II, but were rarely observed in group III. Conclusions: Complement inhibition atone was not enough to alleviate intravascular thrombosis, the main pathology in pulmonary xenotransplantation. Pre-infusion of DDAVP to the donor animal was effective in preventing platelet sequestration and attenuated intravascular thrombosis. It is suggested that the strategies targeting vWF would be promising for successful pulmonary xenotransplantation. (c) 2005 Elsevier B.V. All rights reserved.