title: Novel short-term hypothermic oxygenated perfusion (HOPE) system prevents injury in rat liver graft from non-heart beating donor.
abstract: OBJECTIVE
  To assess a machine perfusion system in rescuing liver grafts from non-heart-beating donors (NHBD).
  
  
  BACKGROUND
  The introduction of extracorporeal liver perfusion systems in the clinical routine depends on feasibility. Conceivably, perfusion could be performed during recipient preparation. We investigated whether a novel rat liver machine perfusion applied after in situ ischemia and cold storage can rescue NHBD liver grafts.
  
  
  METHODS
  We induced cardiac arrest in male Brown Norway rats by phrenotomy and ligation of the subcardial aorta. We studied 2 experimental groups: 45 minutes of warm in situ ischemia + 5 hours cold storage versus 45 minutes of warm in situ ischemia + 5 hours cold storage followed by 1 hour hypothermic oxygenated extracorporeal perfusion (HOPE). In both groups, livers were reperfused in a closed sanguineous isolated liver perfusion device for 3 hours at 37 degrees C. To test the benefit of HOPE on survival, we performed orthotopic liver transplantation in both experimental groups.
  
  
  RESULTS
  After cold storage and reperfusion, NHBD livers showed necrosis of hepatocytes, increased release of AST, and decreased bile flow. HOPE improved NHBD livers significantly with a reduction of necrosis, less AST release, and increased bile flow. ATP was severely depleted in cold-stored NHBD livers but restored in livers treated by HOPE. After orthotopic liver transplantation, grafts treated by HOPE demonstrated a significant extension on animal survival.
  
  
  CONCLUSIONS
  We demonstrate a beneficial effect of HOPE by preventing reperfusion injury in a clinically relevant NHBD model.
authors.affiliation: Swiss Hepato-Pancreato-Biliary (HPB) Center, Laboratory for HPB and Transplantation Surgery, Department of Visceral and Transplantation Surgery, University Hospital Zurich, Zurich, Switzerland. philipp.dutkowski@usz.ch
authors.forename: Philipp
authors.initials: P
authors.lastname: Dutkowski
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Furrer
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Tian
authors.forename: Rolf
authors.initials: R
authors.lastname: Graf
authors.forename: Pierre-Alain
authors.initials: PA
authors.lastname: Clavien
mesh_terms: D000818:Animals; D002102:Cadaver; D050377:Cold Ischemia; D015199:Extracorporeal Membrane Oxygenation / Q000379:methods*; D007036:Hypothermia, Induced; D016031:Liver Transplantation; D008297:Male; D009926:Organ Preservation / Q000379:methods*; D051381:Rats; D020858:Tissue and Organ Harvesting; D052096:Warm Ischemia