Hypothermic Reconditioning by Gaseous Oxygen Improves Survival After Liver Transplantation in the Pig
Hypothermic Reconditioning by Gaseous Oxygen Improves Survival After Liver Transplantation in the Pig
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DOI：
10.1111/j.1600-6143.2011.03731.x
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发表时间：
2011-12-01
影响因子：
8.8
通讯作者：
Paul, A.
中科院分区：
文献类型：
--
作者：
Minor, T.;Koetting, M.;Paul, A.
冷藏肝脏的质量随着缺血时间的延长而下降，原发性天或无功能的风险增加。在这里，我们提供了体内证据，证明先前开发的缺血末期气体氧充气式技术在延长储存时间后对肝移植物复苏的有效性。根据标准的多器官采取方案回收猪肝。对照肝脏在4℃组氨酸色氨酸酮戊二酸溶液中冷藏10 h（冷库[CS]； n = 6）。治疗组（n = 6）肝脏在移植前通过腔静脉充氧进行低温修复（HR） 2 h。通过原位肝移植和1周随访评估生存能力。HR显著改善了移植前的能量电荷和移植后的初始移植物功能。CS后1周存活率为0%，而HR组6头猪中有5头（83%）存活。当时，凝血参数在正常范围内，组织学分析显示治疗后的移植物肝脏组织健康，小梁结构正常。分子分析发现，在HR提供的保护作用中，预防缺血诱导的细胞自噬下降和减轻先天免疫机制（高迁移率组蛋白B1、干扰素- β）是有效机制。
The quality of cold-stored livers declines with the extension of ischemic time and the risk of primary dys- or nonfunction increases. Here, we provide in vivo evidence for the efficacy of the previously developed end-ischemic gaseous oxygen persufflation technique to resuscitate liver grafts after extended storage times. Porcine livers were recovered according to standard multiorgan procurement protocol. Control livers were cold stored in histidine tryptophan ketoglutarate solution for 10 h (cold storage [CS]; n = 6) at 4 degrees C. In the treatment group (n = 6), livers were additionally subjected to hypothermic reconditioning (HR) by gaseous oxygen persufflation via the caval vein for 2 h before transplantation. Viability was assessed by orthotopic liver transplantation and 1 week follow-up. HR significantly improved pretransplant energy charge and initial graft function after transplantation. One week survival after CS was 0% whereas five of six pigs (83%) survived in the HR group. At that time, coagulation parameters were in the normal range and histological analysis disclosed healthy liver tissue with normal trabecular architecture in the treated grafts. Molecular analyses identify the prevention of ischemia-induced decline of cellular autophagy and mitigation of innate immune machinery (high-mobility group protein B1, interferon-beta) as operative mechanisms among the protective effects provided by HR.