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[肝移植供肝热缺血至冷保存耐受时限的实验研究]

[Experimental study on tolerance time limits from warm ischemia to cold preservation of liver grafts].

作者信息

Zheng Shu-guo, Feng Xiao-bin, He Zhen-ping, Qing De-ke, Leng Jian-jun, Dong Jia-hong

机构信息

Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.

出版信息

Zhonghua Gan Zang Bing Za Zhi. 2006 Apr;14(4):250-4.

Abstract

OBJECTIVE

To investigate the tolerance time limits from warm ischemia to cold preservation of liver grafts.

METHODS

Orthotopic liver transplantations (OLTs) were performed on Bama miniature swine. Morphological and functional changes of the liver grafts and biliary tracts after 10 minutes of warm ischemia followed by different durations of cold preservation and its reversibility were investigated.

RESULTS

When the grafts were subjected to 10 minutes of warm ischemia followed by less than 16 hours of cold preservation, all animals could survive 1 week and there was no animal death from biliary necrosis. However, when the cold preservation time exceeded 16 hours, the incidence of biliary necrosis was significantly increased (P<0.05), and recipient death from bile leaks occurred. With further prolongation of the cold preservation time, primary graft nonfunction and intraoperative or early postoperative deaths occurred and the living animals all developed biliary necrosis. When compared with the less than 16 hours cold preservation group, the morphological scores and apoptosis index of the epithelial cells of bile ducts in grafts after reperfusion were significantly elevated in the more than 16 hours cold preservation group (P<0.05) and the activity of Na+-K+-ATPase and Ca2+-ATPase of bile ducts in grafts were also significantly reduced (P<0.05). Liver function tests showed that the recoveries of AST, AST, GGT and ALP were quicker in the 16 hours cold preservation group then those over 16 hour preservation ones. Correlation analysis revealed that the incidence of biliary necrosis was significantly correlated with the morphological score (r = 0.972) and with the apoptosis index of the epithelial cells of bile ducts in grafts after reperfusion (r = 0.931) and also correlated negatively (P<0.01) with the activity of Na+-K+-ATPase (r = -0.973) and Ca2+-ATPase (r = -0.973).

CONCLUSIONS

It is concluded that with 10 minutes of warm ischemia, cold preservation of the grafts should not be longer than 16 hours in order to avoid early biliary necrosis, and the corresponding tolerance time limit of the livers to the cold preservation was less than 20 hours.

摘要

目的

探讨肝移植供肝热缺血至冷保存的耐受时限。

方法

采用巴马小型猪进行原位肝移植。观察热缺血10分钟后不同冷保存时间的供肝及胆管的形态学和功能变化及其可逆性。

结果

供肝热缺血10分钟后冷保存时间小于16小时,所有动物均能存活1周,无动物因胆管坏死死亡。但冷保存时间超过16小时,胆管坏死发生率明显增加(P<0.05),受体因胆漏死亡。随着冷保存时间进一步延长,出现原发性移植肝功能不良及术中或术后早期死亡,存活动物均发生胆管坏死。与冷保存时间小于16小时组比较,冷保存时间超过16小时组再灌注后供肝胆管上皮细胞形态学评分及凋亡指数明显升高(P<0.05),供肝胆管Na+-K+-ATP酶和Ca2+-ATP酶活性明显降低(P<0.05)。肝功能检测显示,冷保存16小时组谷草转氨酶(AST)、谷丙转氨酶(ALT)、γ-谷氨酰转肽酶(GGT)和碱性磷酸酶(ALP)恢复较冷保存时间超过16小时组快。相关性分析显示,胆管坏死发生率与形态学评分(r = 0.972)、再灌注后供肝胆管上皮细胞凋亡指数(r = 0.931)呈显著正相关,与Na+-K+-ATP酶(r = -0.973)和Ca2+-ATP酶(r = -0.973)活性呈显著负相关(P<0.01)。

结论

热缺血10分钟情况下,为避免早期胆管坏死,供肝冷保存时间不应超过16小时,肝脏对冷保存的相应耐受时限小于20小时。

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