Adding the oxygen carrier M101 to a cold-storage solution could be an alternative to HOPE for liver graft preservation

Abstract Background & aims While hypothermic oxygenated machine perfusion (HOPE) is the a promising technique for providing oxygen to the liver during graft preservation, because of associated logistical constraints, addition of an oxygen transporter to simple cold storage solutions (SCS) might be easier. M101 is marine worm hemoglobin that has been shown to improve kidney preservation in the clinic when added to SCS. This study evaluated the effects of the addition of M101 to SCS on the quality of pig liver graft preservation. Methods Pig liver grafts were preserved using SCS, HOPE or SCS+M101 and liver functions compared during cold preservation, as well as after orthotopic allotransplantation (OLT) in pigs. Results During preservation of liver grafts, mitochondrial function, ATP synthesis, anti-oxidant capacities and hepatocyte architecture were better preserved, and free radical production, anti-oxidant activities and inflammatory mediators were lower, with HOPE or SCS+M101 than with SCS alone. However, after one hour of preservation, liver functions with HOPE were superior to those with SCS+M101. After six hours of preservation and OLT, blood levels of aspartate and alanine aminotransferases and lactate dehydrogenase increased with a peak effect at day one post-transplant; values were similar with HOPE and SCS+M101, and were significantly lower than those in the SCS group. At days 1 and 3, tumor necrosis factor α levels remained lower with HOPE and SCS+M101 versus SCS. At day 7, liver cell necrosis and inflammation were less marked in both oxygenated groups. Conclusions When added to SCS, M101 effectively oxygenated liver grafts during preservation, preventing post-transplant injury without reaching the level of HOPE.