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在心脏死亡后供体的临床前模型中,低温机器灌注期间主动充氧对肾脏的益处。

Benefits of active oxygenation during hypothermic machine perfusion of kidneys in a preclinical model of deceased after cardiac death donors.

机构信息

INSERM U1082, Poitiers, France; Université Poitiers, Poitiers, France; CHU Poitiers, Pole UBM, Service de Biochimie, Poitiers, France; FLIRT: Fédération pour L'étude de l'Ischémie Reperfusion en Transplantation, Poitiers, France.

出版信息

J Surg Res. 2013 Oct;184(2):1174-81. doi: 10.1016/j.jss.2013.04.071. Epub 2013 May 21.

Abstract

BACKGROUND

Deceased after cardiac death donors (DCDs) represent a valuable source of organs; however, preventing poor outcome is difficult, even with the use of machine perfusion (MP). It is of paramount importance to improve this method. We proposed to evaluate the benefits of active oxygenation during kidney graft hypothermic MP using a novel perfusion machine: Kidney Assist (KA).

METHODS

We used a pig model of DCD transplantation in Large White pigs. Cold preservation was performed by conventional non-oxygenated MP (KAnoO2) or oxygenated MP (KA).

RESULTS

In the first 2 wk post-transplant, KA grafts displayed a lower serum creatinine peak and a faster return to normal levels compared with KAnoO2 animals, translating into a smaller area under the curve. Urinary neutrophil gelatinase-associated lipocalin levels and serum aspartate amino transferase levels were lower in KA animals compared with the non-oxygenated group. These correlated with better chronic function. Longer follow-up of the animals (3 mo) permitted evaluation of chronic outcome lesions. Interstitial fibrosis was reduced in the KA group, and these kidneys also displayed significantly lower levels of vimentin staining. Further histologic investigation also showed a trend toward decreased chronic inflammation in kidneys preserved with oxygen.

CONCLUSIONS

This new MP system is efficient in preserving DCD kidneys, greatly enhancing the capacity of the graft to withstand preservation stress and improving outcome. Oxygen delivery during preservation is thus valuable for highly damaged organs and offers an important therapeutic tool for transplant teams faced with decreased quality of donor organs.

摘要

背景

心脏死亡供体(DCD)是器官的宝贵来源;然而,即使使用机器灌注(MP),也很难防止不良后果。改进这种方法至关重要。我们提出在使用新型灌注机肾脏辅助(KA)对冷保存期间的肾脏移植物进行主动充氧,以评估其益处。

方法

我们使用大白猪的 DCD 移植猪模型。冷保存通过传统的非充氧 MP(KAnoO2)或充氧 MP(KA)进行。

结果

在移植后的前 2 周,KA 移植物的血清肌酐峰值较低,恢复正常水平的速度较快,曲线下面积较小。与非充氧组相比,KA 动物的尿中性粒细胞明胶酶相关脂质运载蛋白水平和血清天冬氨酸氨基转移酶水平较低。这与更好的慢性功能相关。对动物的更长随访(3 个月)允许评估慢性结果病变。间质纤维化在 KA 组中减少,这些肾脏的波形蛋白染色水平也显著降低。进一步的组织学研究还表明,在充氧保存的肾脏中,慢性炎症减少。

结论

这种新的 MP 系统在保存 DCD 肾脏方面非常有效,大大提高了移植物承受保存应激的能力,并改善了结果。因此,在保存过程中输送氧气对于高度受损的器官很有价值,并为面对供体器官质量下降的移植团队提供了重要的治疗工具。

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