Subnormothermic machine perfusion protects steatotic livers against preservation injury: A potential for donor pool increase?

Abstract

We tested whether rat liver preservation performed by machine perfusion (MP) at 20°C can enhance the functional integrity of steatotic livers versus simple cold storage. We also compared MP at 20°C with hypothermic MP at 8°C, and 4°C. Obese and lean male Zucker rats were used as liver donors. MP was performed for 6 hours with a glucose and N-acetylcysteine-supplemented Krebs-Henseleit solution. Both MP and cold storage preserved livers were reperfused with Krebs-Henseleit solution (2 hours at 37°C). MP at 4°C and 8°C reduced the fatty liver necrosis compared with cold storage but we further protected the organs using MP at 20°C. Necrosis did not differ in livers from lean animals submitted to the different procedures; the enzymes released in steatotic livers preserved by MP at 20°C were similar to those showed in nonsteatotic organs. The adenosine triphosphate/adenosine diphosphate ratio and bile production were higher and the oxidative stress and biliary enzymes were lower in steatotic livers preserved by MP at 20°C as compared with cold storage. In livers from lean rats, the adenosine triphosphate/adenosine diphosphate ratio appears better conserved by MP at 20°C as compared with cold storage. In steatotic livers preserved by cold storage, a 2-fold increase in tumor necrosis factor-alpha levels and caspase-3 activity was observed as compared with organs preserved by MP at 20°C. These data are substantiated by better morphology, higher glycogen content, and lower reactive oxygen species production by sinusoidal cells in steatotic liver submitted to MP at 20°C versus cold storage. MP at 20°C improves cell survival and leads to a marked improvement in hepatic preservation of steatotic livers as compared with cold storage. Liver Transpl 15:20-29, 2009.

Development of a normothermic extracorporeal liver perfusion system toward improving viability and function of human extended criteria donor livers

“…Another approach is the use of subnormothermic machine perfusion (SNMP) with perfusate temperatures at 208C-308C, which is somewhat simpler to perform than normothermic extracorporeal liver perfusion (NELP) from a technical standpoint. (16,17) Importantly, by maintaining 25% of metabolic activity, SNMP allows functional assessment of the liver. (18) Although SNMP has had promising outcomes with DCD liver transplants in animal models, (19) with a considerable reduction in the metabolism rate of the hepatocytes, it may preclude the use of preconditioning modalities such as defatting.…”

Review on Liver Steatosis and its Impact on Liver Transplantation

“…61 On the other hand, the composition of hepatic lipids and particularly thromboxane A 2 levels are considered the principal modulators of I/R injury in the steatotic livers, while the size and morphology of lipid droplets are insignificant. 70 Other potential mechanisms that have been proposed include Kupffer cell dysfunction, 71 more lipid peroxidation, 72,73 more exuberant pro-inflammatory responses, including increased release of pro-inflammatory mediators such as TNF-α, 74 and impaired leukocyte adhesion. 75 Therefore, it is likely that the increased vulnerability of the steatotic livers to more I/R injury are multifactorial, and further experimental studies are required to elucidate the underlying mechanisms.…”

Protective Mechanisms of Hypothermia in Liver Surgery and Transplantation

“…In line with I/R research (25,29), hypothermia (4°C) might not confer additional protection when compared with subnormothermic temperatures (20° to 30°C), whereas subnormothermic temperatures could circumvent the drawbacks associated with deep hypothermia (101). In a rat model of liver transplantation, SNMP at 20°C improved the hepatocellular energy status and reduced ROS formation during reperfusion compared to SCS (101).…”