TY - JOUR
T1 - Metabolomics Differences of the Donor Livers between in Situ and Ex Situ Conditions during Ischemia-free Liver Transplantation
AU - Guo, Zhiyong
AU - Zhan, Liqiang
AU - Gao, Ningxin
AU - Zhang, Zhiheng
AU - Huang, Shanzhou
AU - Wang, Linhe
AU - Zhu, Caihui
AU - Jia, Zehua
AU - Yin, Meixian
AU - Li, Fangcong
AU - Chen, Shirui
AU - Luo, Tao
AU - Liu, Yao
AU - Jia, Yu
AU - Wang, Tielong
AU - Xu, Jinghong
AU - Li, Yuexin
AU - Zhu, Yifan
AU - Chen, Yichao
AU - Yu, Chuhan
AU - Tang, Yunhua
AU - Zhao, Qiang
AU - Wang, Dongping
AU - He, Xiaoshun
N1 - Publisher Copyright:
© 2023 Lippincott Williams and Wilkins. All rights reserved.
PY - 2023/5/1
Y1 - 2023/5/1
N2 - Background. Ischemia-free liver transplantation (IFLT) has been innovated to avoid graft ischemia during organ procurement, preservation, and implantation. However, the metabolism activity of the donor livers between in the in situ and ex situ normothermic machine perfusion (NMP) conditions, and between standard criteria donor and extend criteria donor remains unknown. Methods. During IFLT, plasma samples were collected both at the portal vein and hepatic vein of the donor livers in situ during procurement and ex situ during NMP. An ultra-high performance liquid chromatography-mass spectrometry was conducted to investigate the common and distinct intraliver metabolite exchange. Results. Profound cysteine and methionine metabolism, and aminoacyl-tRNA biosynthesis were found in both in situ and ex situ conditions. However, obvious D-arginine and D-ornithine metabolism, arginine and proline metabolism were only found in the in situ condition. The suppressed activities of the urea cycle pathway during ex situ condition were confirmed in an RNA expression level. In addition, compared with extend criteria donor group, standard criteria donor group had more active intraliver metabolite exchange in metabonomics level. Furthermore, we found that the relative concentration of p-cresol, allocystathionine, L-prolyl-L-proline in the ex situ group was strongly correlated with peak alanine aminotransferase and aspartate aminotransferase at postoperative days 1-7. Conclusions. In the current study, we show the common and distinct metabolism activities during IFLT. These findings might provide insights on how to modify the design of NMP device, improve the perfusate components, and redefine the criteria of graft viability.
AB - Background. Ischemia-free liver transplantation (IFLT) has been innovated to avoid graft ischemia during organ procurement, preservation, and implantation. However, the metabolism activity of the donor livers between in the in situ and ex situ normothermic machine perfusion (NMP) conditions, and between standard criteria donor and extend criteria donor remains unknown. Methods. During IFLT, plasma samples were collected both at the portal vein and hepatic vein of the donor livers in situ during procurement and ex situ during NMP. An ultra-high performance liquid chromatography-mass spectrometry was conducted to investigate the common and distinct intraliver metabolite exchange. Results. Profound cysteine and methionine metabolism, and aminoacyl-tRNA biosynthesis were found in both in situ and ex situ conditions. However, obvious D-arginine and D-ornithine metabolism, arginine and proline metabolism were only found in the in situ condition. The suppressed activities of the urea cycle pathway during ex situ condition were confirmed in an RNA expression level. In addition, compared with extend criteria donor group, standard criteria donor group had more active intraliver metabolite exchange in metabonomics level. Furthermore, we found that the relative concentration of p-cresol, allocystathionine, L-prolyl-L-proline in the ex situ group was strongly correlated with peak alanine aminotransferase and aspartate aminotransferase at postoperative days 1-7. Conclusions. In the current study, we show the common and distinct metabolism activities during IFLT. These findings might provide insights on how to modify the design of NMP device, improve the perfusate components, and redefine the criteria of graft viability.
KW - Humans
KW - Liver Transplantation/methods
KW - Organ Preservation/methods
KW - Living Donors
KW - Tissue and Organ Procurement
KW - Perfusion/methods
KW - Liver/blood supply
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U2 - 10.1097/TP.0000000000004529
DO - 10.1097/TP.0000000000004529
M3 - Article
C2 - 36857152
AN - SCOPUS:85153899539
SN - 0041-1337
VL - 107
SP - E139-E151
JO - Transplantation
JF - Transplantation
IS - 5
ER -