Introduction: Machine perfusion (MP) is becoming the new standard for liver preservation following the successful implementation of devices for kidney and lung preservation ex-vivo. Liver preservation is being performed within a wide temperature range from hypothermia (4[deg]C) to normothermia 37[deg]C. We present here our initial experience with MP under subnormothermic (21[deg]C) conditions using a new HDHBOC specially developed for ex-vivo applications. The new HBOC hasa higher molecular weight and viscosity to limit extravasation into tissues (MW [sim] 1,000 kD, 15 cPs) while engineered for cost-effective production through scalable filtration technology.

Methods: Swine liver allografts (n=6) were preserved for 12 hours with the Liver Assist® device. Tissue and perfusate samples were obtained every 3 hours. The livers were not transplanted and underwent full histological analysis at the completion of the MP protocol. The control group (n=3) was perfused with a bovine-derived HBOC (BDHBOC) and the study group (n=3) was perfused with the HDHBOC. Both groups had a low hemoglobin (Hb) concentration (3g/dL) in the perfusate. Tissue oxygenation (ptO₂) was assessed with oximetry probes inserted in the hepatic parenchyma.

Results: Liver allografts cleared lactate effectively while sustaining a stable pH. The pO₂ were >500 mmHg and ptO₂>200mmHg on both groups. The pCO₂ was lower (<20 mmHg) in the study group. Mitochondrial function (RCR, Maximal Respiratory Rate) was properly sustained on both groups, and levels of ROS (H₂O₂) remained low (<6000 pmol/min/mg) as well as nitrate and nitrite concentrations. The study group remained anatomically intact (histological and EM analysis) throughout the entire duration of the experiments while the control group showed progressive sinusoidal endothelial cell (SEC) damage, early cell detachment and progressive amount of cell debris accumulation in the sinusoids after 9 hours. The 12-hour biopsies showed a significant difference between the 2 groups regarding SEC integrity.

Conclusions: MP with HBOCs at 21[deg]C provides effective oxygenation for liver allografts over a 12-hour period. Despite low Hb concentrations, both HBOCs provided effective oxygenation and CO2 removal over 12 hours. The prolonged use of BDHBOC has a negative impact in SEC and sinusoidal integrity that might affect the liver allograft function after reperfusion. The new HDHBOC appears to correct this complication.

CITATION INFORMATION: Light W. R., Malavalli A., Vandegriff K., Fontes P. Liver Preservation with Machine Perfusion and a New Human-Derived Hemoglobin-Based Oxygen Carrier Solution (HDHBOC) Am J Transplant. 2017;17 (suppl 3).

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