Fatty liver susceptibility to preservation injury using static cold storage versus dynamic machine perfusion

To overcome organ donor shortage, fatty livers could be used, although they appear susceptible to primary-non-function. To understand the mechanisms underlying preservation injury by static Cold-Storage (CS) or dynamic Machine-Perfusion (MP) in fatty livers, we investigated lipidomic profile effects in two rat models of NAFLD: methionine-choline-deficient (MCD) diet and obese Zucker (fa/fa) rats. NAFLD was induced in Wistar rats by 2-week MCD diet; 12-week Zucker rats were also used. Livers were subjected to 6-hour preservation in UW solution at 4°C (CS) or Krebs-Heinseleit solution at 20°C (MP) and 2-hour reperfusion. Hepatic and biliary enzymes release, bile production and ATP/ADP ratio were evaluated. Liver fatty acid (FA) profiling was performed by Mass-Spectrometry (MS). FA analysis showed that in Zucker and MCD rats the total saturated/polyunsaturated fatty acid (PUFA) ratio was 1.5 and 0.71, respectively. MCD rats showed a decrease in saturated stearic acid and polyunsaturated arachidonic acid and an increase in polyunsaturated linoleic acid. Higher AST and LDH release as well as biliary enzymes were found in Zucker versus MCD group after CS; lower bile flow and comparable ATP/ADP ratio were observed in Zucker versus MCD group. No significant differences were detected comparing the MP in MCD versus Zucker rats as observed for hepatic and biliary enzymes release, bile flow and ATP/ADP ratio. Lower hepatic damage and increase bile flow were found in Zucker rat livers after MP as compared with CS. Our results suggest that cellular injury is associated with the liver composition in FAs: Zucker livers with higher levels of saturated FA are more prone to CS injury respect to MCD livers with high PUFA content. The MCD livers appear less susceptible to CS. Thus, the lipidomic profile could be used to choose the appropriate preservation technique to exploit fatty livers for transplantation.