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低温离体灌流对缺血/再灌注损伤和移植结局的保护作用。

Protective effects of hypothermic ex vivo perfusion on ischemia/reperfusion injury and transplant outcomes.

机构信息

Division of Abdominal Organ Transplantation and Molecular Therapies and Organ Preservation Research Laboratory, Department of Surgery Columbia University Medical Center, New York, NY 10032-3784, USA.

出版信息

Transplant Rev (Orlando). 2012 Apr;26(2):163-75. doi: 10.1016/j.trre.2011.09.001. Epub 2011 Nov 8.

DOI:10.1016/j.trre.2011.09.001
PMID:22074785
Abstract

Hypothermic machine preservation (HMP) has been used in renal transplantation since the late 1960s with recent robust prospective, multicenter data showing lower rates of delayed graft function and improved graft survival. Although now clearly beneficial for renal transplantation, extrarenal machine perfusion has remained predominantly in preclinical investigations. Pancreatic HMP has drawn little clinical interest because HMP has been suggested to cause graft edema and congestion, which is associated with early venous thrombosis and graft failure. Early investigation showed no benefit of HMP in whole-organ pancreas transplant. One report did show that HMP increases islet cell yield after isolation. Preclinical work in liver HMP has been promising. Short- and long-term HMP has been shown to improve graft viability and reduce preservation injury, even in animal models of steatotic and donation after cardiac death. The first clinical study of liver HMP using a centrifugal dual perfusion technique showed excellent results with lower hepatocellular injury markers and no adverse perfusion-related outcomes. In addition, a dramatic attenuation of proinflammatory cytokine expression was observed. Further studies of liver HMP are planned with focus on developing a reproducible and standard protocol that will allow the widespread availability of this technology. Future research and clinical trials of novel organ preservation techniques, solutions, and interventions are likely to bring about developments that will allow further reduction of preservation-related ischemia/reperfusion injury and improved outcomes and allow safer utilization of the precious and limited resource of donor organs.

摘要

低温机器保存(HMP)自 20 世纪 60 年代末以来一直用于肾移植,最近有大量强有力的前瞻性多中心数据显示,其延迟移植物功能的发生率较低,移植物存活率提高。尽管现在 HMP 显然对肾移植有益,但器官外机器灌注仍主要停留在临床前研究中。胰腺 HMP 几乎没有引起临床关注,因为 HMP 被认为会导致移植物水肿和淤血,这与早期静脉血栓形成和移植物衰竭有关。早期的研究表明 HMP 对整个器官的胰腺移植没有益处。有一项报告确实表明 HMP 增加了胰岛细胞的产量。肝 HMP 的临床前研究很有希望。短期和长期 HMP 已被证明可提高移植物活力并减少保存损伤,即使在脂肪变性和心脏死亡后供体的动物模型中也是如此。使用离心双灌注技术进行的首例肝 HMP 临床研究取得了优异的结果,肝细胞损伤标志物较低,无不良灌注相关结局。此外,还观察到促炎细胞因子表达明显减弱。正在计划进行更多的肝 HMP 研究,重点是开发一种可重复和标准的方案,使这项技术得到广泛应用。新型器官保存技术、溶液和干预措施的未来研究和临床试验可能会带来新的发展,从而进一步减少保存相关的缺血/再灌注损伤,改善结果,并允许更安全地利用宝贵而有限的供体器官资源。

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