One Hour Hypothermic Oxygenated Perfusion (HOPE) Protects Nonviable Liver Allografts Donated After Cardiac Death

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To test, in a large animal model, the efficacy of machine perfusion to rescue livers after prolonged ischemic injury. Our group previously showed in various rodent models the benefit of endischemic hypothermic oxygenated perfusion (HOPE) in protecting liver injury from donation after cardiac death (DCD). Convincing results are needed in large animal models before application in human. A new model of DCD liver transplantation in large pigs was developed. Pig livers (1300 +/- 210 g each) were harvested 60 minutes after induction of cardiac death (respirator withdrawal). In situ flush and organ procurement were initiated without heparin pretreatment. Then, livers were preserved for 7 hours in cold Celsior (DCD-group) prior to orthotopic transplantation (OLT). Some livers were treated by 1 hour HOPE prior to implantation (HOPE-group). In a first step, animals were kept under anesthesia for 6 hours after orthotopic transplantation. Endpoints included serum (AST) and tissue (ATP, glutathione) markers of injury, bile flow, and histology. In a second step, survival experiments were performed. Livers from the DCD group displayed diffuse necrosis of hepatocytes, increased adhesion of platelets, high AST release, absence of bile flow, depletion of glutathione, and ATP. In contrast, livers treated with HOPE showed dramatic reduction of necrosis, platelet adhesion, while bile flow, ATP recovery and glutathione were improved. Importantly, untreated DCD livers caused graft failure and death of all recipients within 6 hours of reperfusion, whereas HOPE treated DCD livers remained hemodynamically stable. This is the first study in a reliable large animal transplant model demonstrating the efficacy of a simple cold oxygenated machine perfusion system to rescue, otherwise lethal, ischemic injured DCD liver grafts.