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冷缺血损伤对大鼠小肠移植的影响-改良 HTK 溶液的有益作用。

Cold Storage Injury to Rat Small-bowel Transplants-Beneficial Effect of a Modified HTK Solution.

机构信息

Klinik für Anästhesiologie und Operative Intensivmedizin, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany.

Institut für Physiologische Chemie, Universitätsklinikum Essen, Essen, Germany.

出版信息

Transplantation. 2018 Oct;102(10):1666-1673. doi: 10.1097/TP.0000000000002318.

Abstract

BACKGROUND

The small bowel is prone to ischemic injury during transport before transplantation, an injury that endangers the recipient patient. The small-bowel mucosal microcirculation in particular appears to be highly sensitive to injury. Current preservation solutions such as histidine-tryptophan-ketoglutarate (HTK) solution provide some protection to the graft. However, these were developed decades ago and do not address several critical processes, such as hypoxia-induced membrane pores and free radical-mediated hypothermic injury.

METHODS

To protect the graft from cold ischemic injury, we implemented a modified HTK solution here, including glycine, alanine, and iron chelators in a heterotopic, syngeneic small-bowel transplantation model of the rat. The effects of the modified solution and its major components were compared against the conventional HTK solution using intravital microscopy in the early reperfusion period.

RESULTS

The amino acid glycine, added to HTK solution, slightly improved mucosal perfusion. Both, the modified base solution (without iron chelators) and iron chelators increased functional capillary density of the mucosa during the early reperfusion period. The complete modified solution (with glycine, alanine, and iron chelators) significantly increased the perfusion index, functional capillary density of the mucosa, and red blood cell velocity in the grafts after reperfusion in comparison with the grafts preserved with HTK.

CONCLUSIONS

The modified preservation solution improved the microcirculation of the transplants and needs detailed evaluation in further models of small-bowel transplantation.

摘要

背景

在移植前的运输过程中,小肠容易发生缺血性损伤,这会危及受体患者。特别是小肠黏膜微循环似乎对损伤高度敏感。目前的保存液,如组氨酸-色氨酸-酮戊二酸(HTK)溶液,为移植物提供了一些保护。然而,这些都是几十年前开发的,并没有解决几个关键过程,如缺氧诱导的膜孔和自由基介导的低温损伤。

方法

为了防止移植物发生冷缺血损伤,我们在大鼠异位同基因小肠移植模型中实施了改良的 HTK 溶液,其中包括甘氨酸、丙氨酸和铁螯合剂。使用活体显微镜比较改良溶液及其主要成分与传统 HTK 溶液在早期再灌注期间的作用。

结果

添加到 HTK 溶液中的氨基酸甘氨酸略微改善了黏膜灌注。改良基础溶液(不含铁螯合剂)和铁螯合剂都在早期再灌注期间增加了黏膜的功能毛细血管密度。与 HTK 保存的移植物相比,完全改良的溶液(含甘氨酸、丙氨酸和铁螯合剂)在再灌注后显著增加了移植物的灌注指数、黏膜功能毛细血管密度和红细胞速度。

结论

改良的保存液改善了移植物的微循环,需要在进一步的小肠移植模型中进行详细评估。

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