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

1
Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA
2
Division of Transplant Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA
3
Shriners Hospital for Children, Boston, MA 02114, USA
4
Electron Microscopy Research Department, Theodor Bilharz Research Institute, 12411 Giza, Egypt
5
Division of Hepatobiliary Surgery and Liver Transplantation, University Medical Center Groningen, 9700 Groningen, The Netherlands
6
Department of Biomedical Engineering, Rutgers University, Piscataway, NJ 08854, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Metabolites 2019, 9(11), 246; https://doi.org/10.3390/metabo9110246
Received: 23 September 2019 / Revised: 21 October 2019 / Accepted: 22 October 2019 / Published: 24 October 2019
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. View Full-Text
Keywords: steatosis; subnormothermic; normothermic; machine perfusion; anti-oxidant; metabolomics; liver transplantation steatosis; subnormothermic; normothermic; machine perfusion; anti-oxidant; metabolomics; liver transplantation
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Karimian, N.; Raigani, S.; Huang, V.; Nagpal, S.; Hafiz, E.O.A.; Beijert, I.; Mahboub, P.; Porte, R.J.; Uygun, K.; Yarmush, M.; Yeh, H. Subnormothermic Machine Perfusion of Steatotic Livers Results in Increased Energy Charge at the Cost of Anti-Oxidant Capacity Compared to Normothermic Perfusion. Metabolites 2019, 9, 246.

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