title: Potentiation of adverse effects of cold by warm ischemia in circulatory death donors for porcine liver transplantation.
abstract: BACKGROUND
  Wider use of donors after circulatory death (DCD) could reduce mortality on the liver transplantation waiting list. We previously reported that pig livers exposed to ≥ 30 minutes of warm ischemia followed by 4 hours of cold ischemia are at high risk of primary graft nonfunction. We sought to determine how prolonged cold ischemia, after a short, normally well-tolerated period of warm ischemia affects graft function and recipient survival using a porcine model of liver transplantation.
  
  
  METHODS
  Livers were transplanted after exposure to no warm plus 4 hours cold ischemia (group 1); 15 minutes of warm and 4 hours of cold ischemia (group 2); no warm and 8 hours of cold ischemia (group 3); or 15 minutes of warm and 8 hours of cold ischemia (group 4). Recipient survival, graft dysfunction incidence, liver function (prothrombin time), hepatocellular damage (aspartate aminotransferase), sinusoidal cell function (hyaluronic acid), and inflammation (tumor necrosis factor-α) were recorded after transplantation. Biopsies were scored for ischemia-reperfusion injury.
  
  
  RESULTS
  Day 4 survival in group 4 was 0% versus 100%, 83%, and 100% in groups 1, 2, and 3, respectively. Recipients in group 4 exposed to short warm but prolonged cold ischemia displayed severe graft dysfunction, the highest peak transaminase, the greatest inflammatory response, more sinusoidal endothelial cell dysfunction and, the worst histologic score for ischemia-reperfusion injury.
  
  
  CONCLUSIONS
  Liver grafts from DCD donors, even when exposed to short periods of warm ischemia, did not tolerate prolonged cold ischemia well and should be transplanted without delay.
authors.affiliation: Department of Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium. diethard.monbaliu@uzleuven.be
authors.forename: D
authors.initials: D
authors.lastname: Monbaliu
authors.forename: Q
authors.initials: Q
authors.lastname: Liu
authors.forename: K
authors.initials: K
authors.lastname: Vekemans
authors.forename: T
authors.initials: T
authors.lastname: Roskams
authors.forename: J
authors.initials: J
authors.lastname: Pirenne
mesh_terms: D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D050377:Cold Ischemia / Q000009:adverse effects*; D006085:Graft Survival; D006820:Hyaluronic Acid / Q000097:blood; D016031:Liver Transplantation / Q000009:adverse effects*; D023421:Models, Animal; D055031:Primary Graft Dysfunction / Q000097:blood / Q000209:etiology / Q000473:pathology; D011517:Prothrombin Time; D015427:Reperfusion Injury / Q000097:blood / Q000209:etiology* / Q000473:pathology; D012307:Risk Factors; D013552:Swine; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D052096:Warm Ischemia / Q000009:adverse effects*
chemical_list: D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D006820:Hyaluronic Acid; D001219:Aspartate Aminotransferases