title: Warm vs. cold perfusion techniques to rescue rodent liver grafts.
abstract: OBJECTIVE
  A variety of liver perfusion techniques have been proposed to protect liver grafts prior to implantation. We compared hypothermic and normothermic oxygenated perfusion techniques in a rat liver transplant model, using higher risk grafts obtained after cardiac arrest (DCD).
  
  
  METHODS
  Rat livers were subjected to 30 or 60 min in situ warm ischemia, without application of heparin. Livers were excised and stored for 4 h at 4°C, mimicking DCD organ procurement, followed by conventional organ transport. In experimental groups, DCD liver grafts received a 4 h normothermic oxygenated perfusion through the portal vein and the hepatic artery instead of cold storage. The perfusate consisted of either full blood or leukocyte-depleted blood (normothermic groups). Other livers underwent hypothermic oxygenated perfusion (HOPE) for 1 h after warm ischemia and 4 h cold storage (HOPE group). Liver injury was assessed during machine perfusion and after isolated liver reperfusion, and by orthotopic liver transplantation (OLT).
  
  
  RESULTS
  DCD livers, subjected to normothermic perfusion, disclosed reduced injury and improved survival compared to cold storage after limited warm ischemia of 30 min (70%; 7/10), but failed to protect from lethal injury in grafts exposed to 60 min warm ischemia (0%; 0/10). This finding was consistent with Kupffer and endothelial cell activation in cold stored and normothermic perfused livers. In contrast, HOPE protected from hepatocyte and non-parenchymal cell injury and led to 90% (9/10) and 63% (5/8) animal survival after 30 and 60 min of donor warm ischemia, respectively.
  
  
  CONCLUSIONS
  This is the first evidence that HOPE is superior to normothermic oxygenated perfusion in a clinically relevant model through modulation of the innate immunity and endothelial cell activation.
authors.affiliation: Department of Surgery, University Hospital Zurich, Swiss HPB and Transplant Center, Zurich, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Schlegel
authors.affiliation: Department of Surgery, University Hospital Zurich, Swiss HPB and Transplant Center, Zurich, Switzerland.
authors.forename: Philipp
authors.initials: P
authors.lastname: Kron
authors.affiliation: Department of Surgery, University Hospital Zurich, Swiss HPB and Transplant Center, Zurich, Switzerland.
authors.forename: Rolf
authors.initials: R
authors.lastname: Graf
authors.affiliation: Department of Surgery, University Hospital Zurich, Swiss HPB and Transplant Center, Zurich, Switzerland.
authors.forename: Philipp
authors.initials: P
authors.lastname: Dutkowski
authors.affiliation: Department of Surgery, University Hospital Zurich, Swiss HPB and Transplant Center, Zurich, Switzerland. Electronic address: clavien@access.uzh.ch.
authors.forename: Pierre-Alain
authors.initials: PA
authors.lastname: Clavien
mesh_terms: D000818:Animals; D050377:Cold Ischemia; D042783:Endothelial Cells / Q000502:physiology; D007113:Immunity, Innate / Q000502:physiology; D008099:Liver / Q000098:blood supply / Q000473:pathology / Q000502:physiology; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D023421:Models, Animal; D010477:Perfusion / Q000379:methods*; D011914:Rats, Inbred BN; D015996:Survival Rate; D013696:Temperature; D013997:Time Factors; D052096:Warm Ischemia
keywords: DCD liver; Hypothermic oxygenated perfusion; Liver transplantation; Normothermic oxygenated liver perfusion; Survival