Controlled oxygenated rewarming up to normothermia for pretransplant reconditioning of liver grafts

Controlled oxygenated rewarming (COR) up to 20 degrees C during ex vivo machine perfusion limits reperfusion-induced tissue injury upon graft implantation. Rewarming up to normothermia might add further benefits and provide better prediction of post-transplantation organ function. The effect of 90 minutes of oxygenated machine perfusion with Aqix RS-I after cold storage combined with gentle rewarming up to 20 degrees C (COR20) or 35 degrees C (COR35) was studied in rat livers and compared with cold storage alone (CS, n = 6, resp). Postpreservation recovery was evaluated upon warm reperfusion using an established in vitro system. COR generally resulted in significantly improved energetic recovery, increased bile flow, less activities alanine aminotransferase (ALT) release, and improved histopathology upon reperfusion as compared to only cold-stored livers, without significant differences between COR20 and COR35. Parameters obtained during COR, especially during COR35, also allowed for prediction of hepatic recovery upon reperfusion. For instance, ulterior bile production upon reperfusion was found closely correlated to bile flow observed already during COR35 (R-2=0.91). COR significantly improved liver quality after static cold storage. Elevation of machine perfusion temperature up to 35 degrees C may prove promising to refine ex vivo evaluation of the graft prior to transplantation.