Open Access

Appropriate timing for hypothermic machine perfusion to preserve livers donated after circulatory death

  • Authors:
    • Xiaoyan Hu
    • Wei Wang
    • Cheng Zeng
    • Weiyang He
    • Zibiao Zhong
    • Zhongzhong Liu
    • Yanfeng Wang
    • Qifa Ye
  • View Affiliations

  • Published online on: June 18, 2020     https://doi.org/10.3892/mmr.2020.11257
  • Pages: 2003-2011
  • Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hypothermic machine perfusion (HMP) is a method that can be more effective in preserving donor organs compared with cold storage (CS). However, the optimal duration and the exact mechanisms of the protevtive effects of HMP remain unknow. The present study aimed to investigate the adequate perfusion time and mechanisms underlying HMP to protect livers donated after circulatory death (DCD). After circulatory death, adult male Sprague‑Dawley rat livers were subjected to 30 min of warm ischemia (WI) and were subsequently preserved by HMP or CS. To determine the optimal perfusion time, liver tissues were analyzed at 0, 1, 3, 5, 12 and 24 h post‑preservation to evaluate injury and assess the expression of relevant proteins. WI livers were preserved by HMP or CS for 3 h, and liver viability was evaluated by normothermic reperfusion (NR). During NR, oxygen consumption, bile production and the activities of hepatic enzymes in the perfusate were assessed. Following 2 h of NR, levels of inflammation and oxidative stress were determined in the livers and perfusate. HMP for 3 h resulted in the highest expression of myocyte enhancer factor 2C (MEF2C) and kruppel‑like factor 2 (KLF2) and the lowest expression of NF‑κB p65, tumor necrosis factor (TNF)‑α and interleukin (IL)‑1β among the different timepoints, which indicated that 3 h may be the optimal time for HMP induction of the KLF2‑dependent signaling pathway. Compared with CS‑preserved livers, HMP‑preserved livers displayed significantly higher oxygen consumption, lower hepatic enzyme levels in the perfusate following NR. Following HMP preservation, the expression levels of MEF2C, KLF2, endothelial nitric oxide synthase and nitric oxide were increased, whereas the expression levels of NF‑κB p65, IL‑1β and TNF‑α were decreased compared with CS preservation. The results indicated that 3 h may be the optimal time for HMP to protect DCD rat livers. Furthermore, HMP may significantly reduce liver inflammation and oxidative stress injury by mediating the KLF2/NF‑κB/eNOS‑dependent signaling pathway.
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September-2020
Volume 22 Issue 3

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Spandidos Publications style
Hu X, Wang W, Zeng C, He W, Zhong Z, Liu Z, Wang Y and Ye Q: Appropriate timing for hypothermic machine perfusion to preserve livers donated after circulatory death. Mol Med Rep 22: 2003-2011, 2020
APA
Hu, X., Wang, W., Zeng, C., He, W., Zhong, Z., Liu, Z. ... Ye, Q. (2020). Appropriate timing for hypothermic machine perfusion to preserve livers donated after circulatory death. Molecular Medicine Reports, 22, 2003-2011. https://doi.org/10.3892/mmr.2020.11257
MLA
Hu, X., Wang, W., Zeng, C., He, W., Zhong, Z., Liu, Z., Wang, Y., Ye, Q."Appropriate timing for hypothermic machine perfusion to preserve livers donated after circulatory death". Molecular Medicine Reports 22.3 (2020): 2003-2011.
Chicago
Hu, X., Wang, W., Zeng, C., He, W., Zhong, Z., Liu, Z., Wang, Y., Ye, Q."Appropriate timing for hypothermic machine perfusion to preserve livers donated after circulatory death". Molecular Medicine Reports 22, no. 3 (2020): 2003-2011. https://doi.org/10.3892/mmr.2020.11257