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猪肝移植的冷保存、热缺血及己酮可可碱 - UW 溶液

Cold preservation of pig liver grafts with warm ischemia and pentoxifylline-UW solution.

作者信息

Qing De-Ke, Dong Jia-Hong, Han Ben-Li, Chen Xun-Ru

机构信息

Hepatobiliary Surgery Centre of Chengdu Military Unit, Department of Hepatobiliary Surgery, Kunming General Hospital of Chengdu Military Unit of PLA, Kunming City, Yunnan Province, People's Republic of China.

出版信息

Arch Med Res. 2006 May;37(4):449-55. doi: 10.1016/j.arcmed.2005.09.016.

DOI:10.1016/j.arcmed.2005.09.016
PMID:16624641
Abstract

BACKGROUND

We undertook this study to investigate the safe time limits of cold preservation in UW solution of liver grafts subjected to warm ischemia (WI) for 20 min and the changes of the limits when pentoxifylline is added to UW solution.

METHODS

The safe time limit was studied in a simple porcine orthotopic liver transplantation (LTx) model. In donors, livers were subjected to 20 min of WI and subsequent 12-h (group 1, n = 5), 16-h (group 2, n = 5), and 20-h (group 3, n = 3) cold preservation in UW solution, respectively. After the safe time limits were clear, another group (group 4, n = 5) was built to test whether or not the limits can be changed when pentoxifylline is added to UW solution in an unsafe time limit group.

RESULTS

All five animals in group 1 survived up to 7 days of the survey endpoint. In group 2, only one animal survived up to the same survey endpoint and all animals in group 3 died within 12 h. The 1-week survival rate of group 1 was significantly higher than the other two groups. Group 1 had a lower level of alanine aminotransferase (ALT) or aspartase aminotransferase (AST) after LTx, less pathological damage, higher concentration of adenosine triphosphate (ATP) and higher microcirculation blood flux in the grafted liver tissue at 1 h after reperfusion than the other two groups. The results primarily showed that 12-h cold preservation was safe, 16 h was unsafe, and 20 h was highly unsafe. But when pentoxifylline was added to UW solution in cold preservation (16-h group, group 4), in contrast to group 2, the incidence of liver tissue necrosis and primary graft nonfunction was significantly lower in group 4 than in group 2. The 1-week survival rate of the pigs was 100% in the former and 20% in latter group. Levels of ALT and AST in recipients' artery blood, malondialdehyde and TNF-alpha concentration in grafted liver tissue, resistance of portal vein and hepatic artery after preservation in group 4 were significantly reduced, whereas microcirculation blood flux of the grafted liver, superoxide dismutase concentration and ATP concentration in grafted liver tissue were significantly elevated.

CONCLUSIONS

The safe time limit of cold preservation in UW solution of liver grafts subjected to WI for 20 min was about 12 h and the limits can be prolonged to 16 h when pentoxifylline is added to UW solution. Many mechanisms were involved.

摘要

背景

我们开展本研究以探究在UW溶液中经20分钟热缺血(WI)的肝移植供肝冷保存的安全时限,以及在UW溶液中添加己酮可可碱后该时限的变化。

方法

在一个简单的猪原位肝移植(LTx)模型中研究安全时限。在供体中,肝脏先经历20分钟热缺血,随后分别在UW溶液中进行12小时(第1组,n = 5)、16小时(第2组,n = 5)和20小时(第3组,n = 3)的冷保存。明确安全时限后,构建另一组(第4组,n = 5)以测试在不安全时限组的UW溶液中添加己酮可可碱时该时限是否会改变。

结果

第1组的所有5只动物均存活至调查终点的7天。在第2组中,只有1只动物存活至相同的调查终点,第3组的所有动物在12小时内死亡。第1组的1周生存率显著高于其他两组。与其他两组相比,第1组在肝移植后丙氨酸转氨酶(ALT)或天冬氨酸转氨酶(AST)水平较低,病理损伤较小,再灌注后1小时移植肝组织中的三磷酸腺苷(ATP)浓度较高且微循环血流量较高。结果初步表明,12小时冷保存是安全的,16小时是不安全的,20小时是高度不安全的。但是当在冷保存(16小时组,第4组)的UW溶液中添加己酮可可碱时,与第2组相比,第4组肝组织坏死和原发性移植肝无功能的发生率显著降低。前一组猪的1周生存率为100%,后一组为20%。第4组受体动脉血中的ALT和AST水平、移植肝组织中的丙二醛和肿瘤坏死因子-α浓度、保存后的门静脉和肝动脉阻力均显著降低,而移植肝的微循环血流量、移植肝组织中的超氧化物歧化酶浓度和ATP浓度显著升高。

结论

在UW溶液中经20分钟热缺血的肝移植供肝冷保存的安全时限约为12小时,当在UW溶液中添加己酮可可碱时该时限可延长至16小时。其中涉及多种机制。

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