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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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 |
work_keys_str_mv |
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