title: Hepatic preconditioning after prolonged warm ischemia by means of S-adenosyl-L-methionine administration in pig liver transplantation from non-heart-beating donors.
abstract: BACKGROUND
  This study ascertained the effect of S-adenosyl-L-methionine (SAMe) administration on the ischemia-reperfusion injury associated with pig liver transplantation from non-heart-beating donors (NHBDs) after prolonged warm ischemia.
  
  
  METHODS
  Twenty-five animals underwent transplantation with an allograft from an NHBD. After donor cardiac arrest, cardiopulmonary bypass and normothermic recirculation (NR) were performed for 30 min. Ten animals were given SAMe during NR. Donors were cooled to 15 degrees C, and liver procurement was performed.
  
  
  RESULTS
  SAMe reduced histologic liver damage 5 days after transplantation. The necrotic area affected 15.9%+/-14.5% of the liver biopsies in controls and 7.4%+/-9% in SAMe livers. Six of eight controls and only one of eight survivors in the SAMe group developed ischemic cholangitis. SAMe reduced apoptosis of hepatocytes 5 days after transplantation and apoptosis of sinusoidal endothelial cells at reperfusion and at 5 days. SAMe increased energy charge at the end of NR and favored the balance between adenosine and xanthine. It was also associated with higher portal blood flow (740+/-59.2 vs. 475.2+/-65.0 mL/min-1/m-2), hepatic hyaluronic acid extraction (132+/-72.2 vs. -205.8+/-64.6 microg/L), and lower levels of alpha-glutathione-S-transferase after reperfusion (2,601%+/-581% with respect to baseline vs. 6,488%+/-5,612%).
  
  
  CONCLUSIONS
  SAMe administration during liver procurement from NHBDs prevents liver endothelial, parenchymal, and biliary tract damage. The protective role of SAMe may be partially mediated by the effect of adenosine during liver procurement.
authors.affiliation: Transplant Coordination of the Hospital Clínic de Barcelona, Facultat de Medicina, Universitat de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain. mnet@clinic.ub.es
authors.forename: Marc
authors.initials: M
authors.lastname: Net
authors.forename: Ricard
authors.initials: R
authors.lastname: Valero
authors.forename: Raul
authors.initials: R
authors.lastname: Almenara
authors.forename: Ramon
authors.initials: R
authors.lastname: Deulofeu
authors.forename: Miguel A
authors.initials: MA
authors.lastname: López-Boado
authors.forename: Lluis
authors.initials: L
authors.lastname: Capdevila
authors.forename: Pablo
authors.initials: P
authors.lastname: Barros
authors.forename: Josep A
authors.initials: JA
authors.lastname: Bombí
authors.forename: Mercè
authors.initials: M
authors.lastname: Agustí
authors.forename: Ramon
authors.initials: R
authors.lastname: Adalia
authors.forename: Angel
authors.initials: A
authors.lastname: Ruiz
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Arce
authors.forename: Martí
authors.initials: M
authors.lastname: Manyalich
authors.forename: Juan C
authors.initials: JC
authors.lastname: García-Valdecasas
mesh_terms: D000227:Adenine Nucleotides / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002245:Carbon Dioxide / Q000097:blood; D006323:Heart Arrest; D006499:Hepatic Artery; D019194:Ischemic Preconditioning / Q000379:methods*; D008099:Liver / Q000166:cytology* / Q000187:drug effects; D016031:Liver Transplantation / Q000473:pathology / Q000502:physiology*; D023421:Models, Animal; D009336:Necrosis; D010100:Oxygen / Q000097:blood; D011169:Portal Vein; D012436:S-Adenosylmethionine / Q000494:pharmacology*; D013552:Swine; D013997:Time Factors; D014019:Tissue Donors; D014184:Transplantation, Homologous; D019820:Xanthine / Q000378:metabolism
chemical_list: D000227:Adenine Nucleotides; D002245:Carbon Dioxide; D019820:Xanthine; D012436:S-Adenosylmethionine; D000241:Adenosine; D010100:Oxygen