Introduction: There is limited information about the lipid metabolic profile during liver allograft preservation. LP remains a major component of ischemia-reperfusion injuries (IRIs). The aim of this study was to assess metabolic and gene regulatory pathways involved in the lipid catabolism and anabolism during liver preservation.

Methods: Twelve swine liver allografts were divided into two experimental groups comparing SNMP (n=6) with cold storage (CS) (n=6) after 9 hours of cold ischemia time and a 5 day post-operative follow up. SNMP livers were perfused at 21[deg]C with an HBOC solution. Perfusate samples were taken at hourly intervals from both groups and checked for concentrations of 52 lipid-related metabolites. 135 additional lipid analytes were assessed post-operatively in the bile. Liver tissue biopsies were obtained every 3 hours and SNMP livers had 25,000 genes assessed by microarrays.

Results: The byproducts of β-oxidation of fatty acids such as ketone bodies (3-hydroxybutyrate (↑7folds, p=0.006) and acetoacetate (↑20folds, p<0.001)) were significantly higher in the SNMP group. In addition, carnitine (p=0.007) and acetyl carnitine (p=0.04) levels were significantly lower in the SNMP livers. Lipogenesis was downregulated in the SNMP group as evident by: 1) significantly lower levels of long-chain fatty acids: oleate (p<0.001), eicosenoate (p<0.001), and dihomo-linoleate (p=0.003); 2) slightly higher mead acid levels (p>0.05); 3) significantly lower triglycerides metabolism byproducts: ethanolamine (p=0.02) and glycerophosphoylcholine (p=0.0002). Lysolipids levels were significantly higher in the SNMP and sphingolipids were significantly higher in the CS groups, showing indirect signs of cell membrane integrity and downregulation of lipid peroxidation in the SNMP group. Microarray analysis revealed reduction in the expression of genes involved in the fatty acid and triglyceride synthesis during SNMP.

Conclusion: Liver allografts preserved by SNMP/HBOC experienced a shift on the hepatic lipid metabolic profile from fatty acid synthesis towards β-oxidation as a way to produce energy. In addition, SNMP leads to significant reduction in lipogenesis. SNMP appears to minimize lipid peroxidation when compared to CS.

CITATION INFORMATION: Banan B, Lopez R, Hughes C, Michalopoulos G, Fontes P. Subnormothermic Machine Perfusion (SNMP) of Liver Allografts with a Novel Hemoglobin-Based Oxygen Carrier (HBOC) Increases β-Oxidation of Fatty Acids and Decreases Lipid Peroxidation (LP). Am J Transplant. 2016;16 (suppl 3).

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