Subnormothermic Machine Perfusion of Steatotic Livers Results in Increased Energy Charge at the Cost of Anti-Oxidant Capacity Compared to Normothermic Perfusion
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
Affiliations
Negin Karimian
Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA
Siavash Raigani
Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA
Viola Huang
Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA
Sonal Nagpal
Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA
Ehab O. A. Hafiz
Electron Microscopy Research Department, Theodor Bilharz Research Institute, 12411 Giza, Egypt
Irene Beijert
Division of Hepatobiliary Surgery and Liver Transplantation, University Medical Center Groningen, 9700 Groningen, The Netherlands
Paria Mahboub
Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA
Robert J. Porte
Division of Hepatobiliary Surgery and Liver Transplantation, University Medical Center Groningen, 9700 Groningen, The Netherlands
Korkut Uygun
Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA
Martin Yarmush
Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA
Heidi Yeh
Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA
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.
