title: Effects of ischemic preconditioning in a pig model of large-for-size liver transplantation.
abstract: OBJECTIVE
  In most cases of pediatric liver transplantation, the clinical scenario of large-for-size transplants can lead to hepatic dysfunction and a decreased blood supply to the liver graft. The objective of the present experimental investigation was to evaluate the effects of ischemic preconditioning on this clinical entity.
  
  
  METHODS
  Eighteen pigs were divided into three groups and underwent liver transplantation: a control group, in which the weights of the donors were similar to those of the recipients, a large-for-size group, and a large-for-size + ischemic preconditioning group. Blood samples were collected from the recipients to evaluate the pH and the sodium, potassium, aspartate aminotransferase and alanine aminotransferase levels. In addition, hepatic tissue was sampled from the recipients for histological evaluation, immunohistochemical analyses to detect hepatocyte apoptosis and proliferation and molecular analyses to evaluate the gene expression of Bax (pro-apoptotic), Bcl-XL (anti-apoptotic), c-Fos and c-Jun (immediate-early genes), ischemia-reperfusion-related inflammatory cytokines (IL-1, TNF-alpha and IL-6, which is also a stimulator of hepatocyte regeneration), intracellular adhesion molecule, endothelial nitric oxide synthase (a mediator of the protective effect of ischemic preconditioning) and TGF-beta (a pro-fibrogenic cytokine).
  
  
  RESULTS
  All animals developed acidosis. At 1 hour and 3 hours after reperfusion, the animals in the large-for-size and large-for-size + ischemic preconditioning groups had decreased serum levels of Na and increased serum levels of K and aspartate aminotransferase compared with the control group. The molecular analysis revealed higher expression of the Bax, TNF-alpha, I-CAM and TGF-beta genes in the large-for-size group compared with the control and large-for-size + ischemic preconditioning groups. Ischemic preconditioning was responsible for an increase in c-Fos, IL-1, IL-6 and e-NOS gene expression.
  
  
  CONCLUSIONS
  Ischemia-reperfusion injury in this model of large-for-size liver transplantation could be partially attenuated by ischemic preconditioning.
authors: Pediatric Liver Transplantation Unit and Laboratory of Research in Pediatric Surgery (LIM 30), Pediatric Surgery Division, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
authors: Antonio José Gonçalves
authors: AJ
authors: Leal
authors: Pediatric Liver Transplantation Unit and Laboratory of Research in Pediatric Surgery (LIM 30), Pediatric Surgery Division, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
authors: Ana Cristina Aoun
authors: AC
authors: Tannuri
authors: Department of Surgical Technique and Experimental Surgery, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
authors: Alessandro Rodrigo
authors: AR
authors: Belon
authors: Pediatric Liver Transplantation Unit and Laboratory of Research in Pediatric Surgery (LIM 30), Pediatric Surgery Division, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
authors: Raimundo Renato Nunes
authors: RR
authors: Guimarães
authors: Pediatric Liver Transplantation Unit and Laboratory of Research in Pediatric Surgery (LIM 30), Pediatric Surgery Division, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
authors: Maria Cecília Mendonça
authors: MC
authors: Coelho
authors: Pediatric Liver Transplantation Unit and Laboratory of Research in Pediatric Surgery (LIM 30), Pediatric Surgery Division, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
authors: Josiane de Oliveira
authors: Jde O
authors: Gonçalves
authors: Pediatric Liver Transplantation Unit and Laboratory of Research in Pediatric Surgery (LIM 30), Pediatric Surgery Division, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
authors: Suellen
authors: S
authors: Serafini
authors: Liver Function Research Laboratory (LIM-14), Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
authors: Evandro Sobroza de
authors: ES
authors: Melo
authors: Pediatric Liver Transplantation Unit and Laboratory of Research in Pediatric Surgery (LIM 30), Pediatric Surgery Division, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
authors: Uenis
authors: U
authors: Tannuri
mesh_terms: D000138:Acidosis / Q000150:complications; D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001219:Aspartate Aminotransferases / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D015870:Gene Expression; D022781:Hepatocytes / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D019194:Ischemic Preconditioning / Q000379:methods*; D008099:Liver / Q000033:anatomy & histology / Q000098:blood supply*; D016031:Liver Transplantation / Q000009:adverse effects / Q000379:methods*; D023421:Models, Animal; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009929:Organ Size; D011188:Potassium / Q000097:blood; D011897:Random Allocation; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012964:Sodium / Q000097:blood; D013552:Swine; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D012964:Sodium; D019001:Nitric Oxide Synthase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D011188:Potassium