title: The effect of brain death in rat steatotic and non-steatotic liver transplantation with previous ischemic preconditioning.
abstract: OBJECTIVE
  Most liver grafts undergoing transplantation derive from brain dead donors, which may also show hepatic steatosis, being both characteristic risk factors in liver transplantation. Ischemic preconditioning shows benefits when applied in non-brain dead clinical situations like hepatectomies, whereas it has been less promising in the transplantation from brain dead patients. This study examined how brain death affects preconditioned steatotic and non-steatotic liver grafts undergoing transplantation.
  
  
  METHODS
  Steatotic and non-steatotic grafts from non-brain dead and brain dead-donors were cold stored for 6h and then transplanted. After 2, 4, and 16 h of reperfusion, hepatic damage was analysed. In addition, two therapeutic strategies, ischemic preconditioning and/or acetylcholine pre-treatment, and their underlying mechanisms were characterized.
  
  
  RESULTS
  Preconditioning benefits in non-brain dead donors were associated with nitric oxide and acetylcholine generation. In brain dead donors, preconditioning generated nitric oxide but did not promote acetylcholine upregulation, and this resulted in inflammation and damage. Acetylcholine treatment in brain dead donors, through PKC, increased antioxidants and reduced lipid peroxidation, nitrotyrosines and neutrophil accumulation, altogether protecting against damage. The combination of acetylcholine and preconditioning conferred stronger protection against damage, oxidative stress and neutrophil accumulation than acetylcholine treatment alone. These superior beneficial effects were due to a selective preconditioning-mediated generation of nitric oxide and regulation of PPAR and TLR4 pathways, which were not observed when acetylcholine was administered alone.
  
  
  CONCLUSIONS
  Our findings propose the combination of acetylcholine+preconditioning as a feasible and highly protective strategy to reduce the adverse effects of brain death and to ultimately improve liver graft quality.
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Mónica B
authors.initials: MB
authors.lastname: Jiménez-Castro
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Noelia
authors.initials: N
authors.lastname: Meroño
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Mariana
authors.initials: M
authors.lastname: Mendes-Braz
authors.affiliation: Barcelona Hepatic Hemodynamic Laboratory, IDIBAPS, CIBEREHD, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Gracia-Sancho
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Laia
authors.initials: L
authors.lastname: Martínez-Carreres
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Maria Eugenia
authors.initials: ME
authors.lastname: Cornide-Petronio
authors.affiliation: Hospital Regional de Alta Especialidad de Ciudad Victoria, Ciudad Victoria, Mexico.
authors.forename: Araní
authors.initials: A
authors.lastname: Casillas-Ramirez
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Liver Unit, Hospital Clínic, Barcelona, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Rodés
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. Electronic address: cperalta@clinic.ub.es.
authors.forename: Carmen
authors.initials: C
authors.lastname: Peralta
mesh_terms: D000818:Animals; D001926:Brain Death; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D019194:Ischemic Preconditioning / Q000379:methods*; D016031:Liver Transplantation; D018384:Oxidative Stress; D051381:Rats; D011924:Rats, Zucker
keywords: Acetylcholine; Brain death; Ischemic preconditioning; Liver transplantation; Nitric oxide; Steatotic liver grafts