Comparative evaluation of distinct dual hypothermic oxygenated perfusion strategies in a porcine donation after...

There is increasing clinical evidence for the protective effect of the hypothermic oxygenated perfusion (HOPE) treatment strategy in human donation after circulatory death (DCD) liver transplantation. HOPE treatment is routinely applied for 2 hours after static cold storage (SCS). This study aimed to determine the optimal timing and duration of HOPE treatment by comparing different HOPE treatment strategies in a porcine DCD liver transplantation model. Donor livers from Tibetan miniature pigs underwent 60-minute warm ischemia and were then randomized into 4 groups according to different preservation strategies, including SCS treatment, upfront HOPE (U-HOPE), end-ischemic HOPE (E-HOPE), and continuous HOPE (C-HOPE) treatment groups (n = 6 per group). All these livers were transplanted orthotopically. Posttransplant survival and graft ischemia-reperfusion injury were assessed during a 7-day follow-up. The 7-day survival rates were 0% for the SCS treatment group, 33.3% (2/6) for the U-HOPE treatment group, and 100.0% (6/6) for both E-HOPE and C-HOPE treatment groups. Compared with the SCS treatment strategy, all HOPE treatment strategies enhanced lactate clearance and liver function recovery, reduced oxidative stress and inflammatory responses, reduced hepatocellular and biliary injury, and protected mitochondrial function. Importantly, such protective effects were more pronounced in the livers undergoing E-HOPE and C-HOPE treatments than in U-HOPE treatments. All HOPE treatment approaches showed superior preservation of DCD livers over SCS. Among them, the E-HOPE and C-HOPE treatments achieved improved short-term survival and enhanced protection against graft ischemia-reperfusion injury in comparison with the U-HOPE treatment.