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

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

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...

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Main Authors: Negin Karimian, Siavash Raigani, Viola Huang, Sonal Nagpal, Ehab O. A. Hafiz, Irene Beijert, Paria Mahboub, Robert J. Porte, Korkut Uygun, Martin Yarmush, Heidi Yeh
Format: Article
Language:English
Published: MDPI AG 2019-10-01
Series:Metabolites
Subjects:
steatosis
subnormothermic
normothermic
machine perfusion
anti-oxidant
metabolomics
liver transplantation
Online Access:https://www.mdpi.com/2218-1989/9/11/246
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spelling doaj-856e38fb5930489681fd12020c85722b2020-11-25T01:54:57ZengMDPI AGMetabolites2218-19892019-10-0191124610.3390/metabo9110246metabo9110246Subnormothermic Machine Perfusion of Steatotic Livers Results in Increased Energy Charge at the Cost of Anti-Oxidant Capacity Compared to Normothermic PerfusionNegin Karimian0Siavash Raigani1Viola Huang2Sonal Nagpal3Ehab O. A. Hafiz4Irene Beijert5Paria Mahboub6Robert J. Porte7Korkut Uygun8Martin Yarmush9Heidi Yeh10Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USACenter for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USACenter for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USACenter for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USAElectron Microscopy Research Department, Theodor Bilharz Research Institute, 12411 Giza, EgyptDivision of Hepatobiliary Surgery and Liver Transplantation, University Medical Center Groningen, 9700 Groningen, The NetherlandsCenter for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USADivision of Hepatobiliary Surgery and Liver Transplantation, University Medical Center Groningen, 9700 Groningen, The NetherlandsCenter for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USACenter for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USACenter for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USAThere 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.https://www.mdpi.com/2218-1989/9/11/246steatosissubnormothermicnormothermicmachine perfusionanti-oxidantmetabolomicsliver transplantation
collection DOAJ
language English
format Article
sources DOAJ
author Negin Karimian
Siavash Raigani
Viola Huang
Sonal Nagpal
Ehab O. A. Hafiz
Irene Beijert
Paria Mahboub
Robert J. Porte
Korkut Uygun
Martin Yarmush
Heidi Yeh
spellingShingle Negin Karimian
Siavash Raigani
Viola Huang
Sonal Nagpal
Ehab O. A. Hafiz
Irene Beijert
Paria Mahboub
Robert J. Porte
Korkut Uygun
Martin Yarmush
Heidi Yeh
Subnormothermic Machine Perfusion of Steatotic Livers Results in Increased Energy Charge at the Cost of Anti-Oxidant Capacity Compared to Normothermic Perfusion
Metabolites
steatosis
subnormothermic
normothermic
machine perfusion
anti-oxidant
metabolomics
liver transplantation
author_facet Negin Karimian
Siavash Raigani
Viola Huang
Sonal Nagpal
Ehab O. A. Hafiz
Irene Beijert
Paria Mahboub
Robert J. Porte
Korkut Uygun
Martin Yarmush
Heidi Yeh
author_sort Negin Karimian
title Subnormothermic Machine Perfusion of Steatotic Livers Results in Increased Energy Charge at the Cost of Anti-Oxidant Capacity Compared to Normothermic Perfusion
title_short Subnormothermic Machine Perfusion of Steatotic Livers Results in Increased Energy Charge at the Cost of Anti-Oxidant Capacity Compared to Normothermic Perfusion
title_full Subnormothermic Machine Perfusion of Steatotic Livers Results in Increased Energy Charge at the Cost of Anti-Oxidant Capacity Compared to Normothermic Perfusion
title_fullStr Subnormothermic Machine Perfusion of Steatotic Livers Results in Increased Energy Charge at the Cost of Anti-Oxidant Capacity Compared to Normothermic Perfusion
title_full_unstemmed Subnormothermic Machine Perfusion of Steatotic Livers Results in Increased Energy Charge at the Cost of Anti-Oxidant Capacity Compared to Normothermic Perfusion
title_sort subnormothermic machine perfusion of steatotic livers results in increased energy charge at the cost of anti-oxidant capacity compared to normothermic perfusion
publisher MDPI AG
series Metabolites
issn 2218-1989
publishDate 2019-10-01
description 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.
topic steatosis
subnormothermic
normothermic
machine perfusion
anti-oxidant
metabolomics
liver transplantation
url https://www.mdpi.com/2218-1989/9/11/246
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AT siavashraigani subnormothermicmachineperfusionofsteatoticliversresultsinincreasedenergychargeatthecostofantioxidantcapacitycomparedtonormothermicperfusion
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AT irenebeijert subnormothermicmachineperfusionofsteatoticliversresultsinincreasedenergychargeatthecostofantioxidantcapacitycomparedtonormothermicperfusion
AT pariamahboub subnormothermicmachineperfusionofsteatoticliversresultsinincreasedenergychargeatthecostofantioxidantcapacitycomparedtonormothermicperfusion
AT robertjporte subnormothermicmachineperfusionofsteatoticliversresultsinincreasedenergychargeatthecostofantioxidantcapacitycomparedtonormothermicperfusion
AT korkutuygun subnormothermicmachineperfusionofsteatoticliversresultsinincreasedenergychargeatthecostofantioxidantcapacitycomparedtonormothermicperfusion
AT martinyarmush subnormothermicmachineperfusionofsteatoticliversresultsinincreasedenergychargeatthecostofantioxidantcapacitycomparedtonormothermicperfusion
AT heidiyeh subnormothermicmachineperfusionofsteatoticliversresultsinincreasedenergychargeatthecostofantioxidantcapacitycomparedtonormothermicperfusion
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