Subnormothermic Machine Perfusion of Steatotic Livers Results in Increased Energy Charge at the Cost of Anti-Oxidant Capacity Compared to Normothermic Perfusion

被引：15

作者：

Karimian, Negin ^{[1
,2
,3
]}

Raigani, Siavash ^{[1
,2
,3
]}

Huang, Viola ^{[1
,3
]}

Nagpal, Sonal ^{[1
,3
]}

Hafiz, Ehab O. A. ^{[4
]}

Beijert, Irene ^{[5
]}

Mahboub, Paria ^{[1
,3
]}

Porte, Robert J. ^{[5
]}

Uygun, Korkut ^{[1
,2
,3
]}

Yarmush, Martin ^{[1
,3
,6
]}

Yeh, Heidi ^{[1
,2
,3
]}

机构：

[1] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02115 USA

[2] Harvard Med Sch, Massachusetts Gen Hosp, Div Transplant Surg, Boston, MA 02115 USA

[3] Shriners Hosp Children, Boston, MA 02114 USA

[4] Theodor Bilharz Res Inst, Electron Microscopy Res Dept, Giza 12411, Egypt

[5] Univ Med Ctr Groningen, Div Hepatobiliary Surg & Liver Transplantat, NL-9700 Groningen, Netherlands

[6] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA

来源：

METABOLITES | 2019年 / 9卷 / 11期

基金：

美国国家卫生研究院;

关键词：

steatosis; subnormothermic; normothermic; machine perfusion; anti-oxidant; metabolomics; liver transplantation; OXIDATIVE STRESS; TRANSPLANTATION; METABOLOMICS; REPERFUSION; GLUTATHIONE; INHIBITION; GRAFTS; SYSTEM; TARGET; ACID;

D O I：

10.3390/metabo9110246

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

There continues to be significant debate regarding the most effective mode of ex situ machine perfusion of livers for transplantation. Subnormothermic (SNMP) and normothermic machine perfusion (NMP) are two methods with different benefits. We examined the metabolomic profiles of discarded steatotic human livers during three hours of subnormothermic or normothermic machine perfusion. Steatotic livers regenerate higher stores of ATP during SNMP than NMP. However, there is a significant depletion of available glutathione during SNMP, likely due to an inability to overcome the high energy threshold needed to synthesize glutathione. This highlights the increased oxidative stress apparent in steatotic livers. Rescue of discarded steatotic livers with machine perfusion may require the optimization of redox status through repletion or supplementation of reducing agents.

引用

页数：13

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