Comparative Evaluation of Distinct Dual Hypothermic Oxygenated Perfusion Strategies in a Porcine DCD Liver Transplantation Model

Abstract There is increasing clinical evidence for the protective effect of hypothermic oxygenated perfusion (HOPE) in human donation after circulatory death (DCD) liver transplantation. HOPE is routinely applied for two hours after static cold storage (SCS). This study aimed to determine the optimal timing and duration of HOPE by comparing different HOPE strategies in a porcine DCD liver transplantation model. Donor livers from Tibetan miniature pigs underwent 60-min warm ischemia and then were randomized into four groups according to different preservation strategies, including SCS, upfront HOPE (U-HOPE), end-ischemic HOPE (E-HOPE) and continuous HOPE (C-HOPE) groups (n=6 per group). All these livers were transplanted orthotopically. Post-transplant survival and graft ischemia-reperfusion injury were assessed during a 7-day follow-up. The 7-day survival rates were 0% for SCS, 33.3% (2/6) for U-HOPE, and 100.0% (6/6) for both E-HOPE and C-HOPE groups. Compared with SCS, all HOPE 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 end-ischemic and continuous HOPE than upfront HOPE. All HOPE approaches showed superior preservation of DCD livers over SCS. Among them, end-ischemic and continuous HOPE achieve improved short-term survival and enhanced protection of graft IRI in comparison to upfront HOPE.