Subnormothermic Machine Perfusion Protects Against Rat Liver Preservation Injury: A Comparative Evaluation With Conventional Cold Storage

Abstract 

Hypothermic machine perfusion (MP) of the liver has been reported to improve graft function reclaiming marginal livers, such as those from non–heart-beating donors. Livers from obese donors often have fatty infiltrates and are more susceptible to hypothermic conditions. No data exist about MP at temperatures >4°C. This study evaluated liver function after organ preservation by comparing MP at 20°C with conventional cold storage.

Methods

For MP, rat livers were perfused for 6 hours using an oxygenated Krebs-Henseleit (KH) solution at 20°C (pH 7.4). For cold storage, livers were perfused in situ and preserved with Celsior solution at 4°C for 6 hours. The reperfusion period with KH (2 hours at 37°C) was performed under the same conditions both among livers preserved by MP or cold storage. Hepatic enzyme release (aspartate aminotransferase [AST], alanine aminotransferase [ALT], lactate dehydrogenase [LDH], and γ-glutamyl transferase [GGT]), bile production, and ATP levels were measured during MP and reperfusion.

Results

At the end of reperfusion, livers preserved by MP showed significantly decreased liver damage compared with cold storage: AST, 18 ± 4 vs. 45 ± 6 mU/mL (P < .01); ALT, 1.5 ± .07 vs. 6 ± 0.5 mU/mL (P < .01); and LDH, 82 ± 2 vs. 135 ± 29 mU/mL (P < .05). No difference was observed between bile production between MP and cold storage. High levels of biliary GGT and LDH were found in cold preserved livers. ATP levels were higher in livers preserved with MP compared with those preserved by cold storage.

Conclusions

MP at 20°C resulted in a better quality of liver preservation, improving hepatocyte survival, compared with conventional cold storage. This may provide a new method for successful utilization of marginal livers, in particular fatty livers.