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

Negin Karimian,Korkut Uygun,Heidi Yeh,Ehab O A Hafiz,Viola Huang,Robert J Porte,Paria Mahboub,Sonal Nagpal,Irene Beijert,Martin Yarmush,Siavash Raigani

doi:10.3390/metabo9110246

Abstract

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.

Highlights

Liver transplantation remains the only definitive cure for end-stage liver disease
normothermic machine perfusion (NMP) livers cleared lactate at a faster rate compared to subnormothermic machine perfusion (SNMP) livers, which became significant after
Glucose levels in the perfusate were significantly higher in the NMP group after 60 min of perfusion compared to the SNMP group

Summary

Introduction

Liver transplantation remains the only definitive cure for end-stage liver disease. Despite significant success and innovation in the field, there continues to be a severe shortage of organs that is unable to meet the need of transplant candidates. There is a significant range of perfusion practices among different centers. Groups have reported their experience with NMP [2,3,4], subnormothermic machine perfusion (SNMP) [5,6,7], and hypothermic oxygenated perfusion (HOPE) [8,9], each with its own unique benefits and deficits. There is no consensus on the best approach for machine perfusion of livers This is further complicated by the heterogeneity of donor livers, which include donation after cardiac death (DCD), steatotic grafts, and other extended-criteria (or marginal) donor characteristics, each of which may benefit from a different application of machine perfusion

Methods

Results

Conclusion