title: The differential tissue expression of inflammatory, oxidative stress, and apoptosis markers in human uncontrolled non-heart-beating donors.
abstract: BACKGROUND
  Uncontrolled non-heart-beating donor (UNHBD) transplantation offers a major opportunity to ameliorate the effects of the donor shortage. However, little is known about the true status of the organs obtained from these donors. UNHBD transplantation is performed under unfavorable conditions and involves exposure to several harmful stimuli that have been identified as triggers for immediate inflammatory response, oxidative stress, and apoptotic phenomena. This adverse scenario could explain the higher rates of graft dysfunction due to primary nonfunction traditionally observed in NHBD. Our aim was to assess the expression of proinflammatory, oxidative, and apoptotic markers in liver, lung, and pancreas tissue samples obtained from UNHBD and to compare these expression levels with those observed in brain-dead donors (BDD).
  
  
  METHODS
  Samples from human type 2 NHBD and BDD were obtained at the end of cold storage. Interleukin (IL)-1β, tumor necrosis factor-α, IL-6, IL-10, endothelial nitric oxide synthase, inducible nitric oxide synthase, type 1 heme oxygenase, type 2 heme oxygenase, Bax, and Bcl-2 protein and mRNA expression, as well as catalase, glutathione peroxidase, and glutathione reductase tissue activity, were determined.
  
  
  RESULTS
  UNHBD showed similar or lower expression of proinflammatory mediators and apoptosis markers in all three organs without modifications to the anti-inflammatory cytokines. Although the major oxidative stress marker levels were also comparable in both types of donors, the type 1 heme oxygenase mRNA expression and antioxidant enzyme activity were slightly diminished in UNHBD.
  
  
  CONCLUSIONS
  The initial tissue damage generated during the UNHB donation process is at least comparable with that observed in BDD. However, although the expression of the immediate immune response and apoptosis markers is similar, a mild impairment of the local antioxidant activity was observed.
authors.affiliation: Department of Surgery, Germans Trias i Pujol Hospital-Universitat Autònoma, Barcelona, Spain. balibrea@gmail.com
authors.forename: José M
authors.initials: JM
authors.lastname: Balibrea
authors.forename: José R
authors.initials: JR
authors.lastname: Núñez-Peña
authors.forename: María C
authors.initials: MC
authors.lastname: García-Martín
authors.forename: Yoko
authors.initials: Y
authors.lastname: Olmedilla
authors.forename: Esteban
authors.initials: E
authors.lastname: Martín-Antona
authors.forename: Jeremy
authors.initials: J
authors.lastname: Berthuin
authors.forename: Lisa
authors.initials: L
authors.lastname: Rancan
authors.forename: Eleva
authors.initials: E
authors.lastname: Vara
authors.forename: José L
authors.initials: JL
authors.lastname: Balibrea
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D002102:Cadaver; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006323:Heart Arrest / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D010179:Pancreas / Q000378:metabolism* / Q000473:pathology; D014019:Tissue Donors; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D016207:Cytokines; D051028:bcl-2-Associated X Protein; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2