title: Variable activation of phosphoinositide 3-kinase influences the response of liver grafts to ischemic preconditioning.
abstract: OBJECTIVE
  The efficacy of ischemic preconditioning (IPC) in preventing reperfusion injury in human liver transplants is still questioned. Phosphoinositide-3-kinase (PI3K) is essential for IPC development in rodent livers. This work investigates whether PI3K-dependent signals might account for the inconsistent responses to IPC of transplanted human livers.
  
  
  METHODS
  Forty livers from deceased donors were randomized to receive or not IPC before recovery. PI3K activation was evaluated in biopsies obtained immediately before IPC and 2 h after reperfusion by measuring the phosphorylation of the PI3K downstream kinase PKB/Akt and the levels of the PI3K antagonist phosphatase tensin-homologue deleted from chromosome 10 (PTEN).
  
  
  RESULTS
  IPC increased PKB/Akt phosphorylation (p = 0.01) and decreased PTEN levels (p = 0.03) in grafts, but did not significantly ameliorate post-transplant reperfusion injury. By calculating T(2h)/T(0) PKB/Akt phosphorylation ratios, 10/19 (53%) of the preconditioned grafts had ratios above the control threshold (IPC-responsive), while the remaining nine grafts showed ratios comparable to controls (IPC-non-responsive). T(2h)/T(0) PTEN ratios were also decreased (p < or = 0.03) only in IPC-responsive grafts. The patients receiving IPC-responsive organs had ameliorated (p < or = 0.05) post-transplant aminotransferase and bilirubin levels, while prothrombin activity was unchanged.
  
  
  CONCLUSIONS
  Impaired PI3K signaling might account for the variability in the responses to IPC of human grafts from deceased donors.
authors.affiliation: Department of General Surgery and Organ Transplantation, Liver and Multiorgan Transplant Unit, Alma Mater Studiorum University of Bologna, Bologna, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Cescon
authors.forename: Rita
authors.initials: R
authors.lastname: Carini
authors.forename: Gianluca
authors.initials: G
authors.lastname: Grazi
authors.forename: Paolo
authors.initials: P
authors.lastname: Caraceni
authors.forename: Elisa
authors.initials: E
authors.lastname: Alchera
authors.forename: Giorgio
authors.initials: G
authors.lastname: Gasloli
authors.forename: Matteo
authors.initials: M
authors.lastname: Ravaioli
authors.forename: Francesco
authors.initials: F
authors.lastname: Tuci
authors.forename: Chiara
authors.initials: C
authors.lastname: Imarisio
authors.forename: Caterina
authors.initials: C
authors.lastname: Dal Ponte
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Pertosa
authors.forename: Mauro
authors.initials: M
authors.lastname: Bernardi
authors.forename: Antonio D
authors.initials: AD
authors.lastname: Pinna
authors.forename: Emanuele
authors.initials: E
authors.lastname: Albano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D005260:Female; D006801:Humans; D019194:Ischemic Preconditioning; D008099:Liver / Q000201:enzymology / Q000473:pathology; D016031:Liver Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000378:metabolism / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015427:Reperfusion Injury / Q000517:prevention & control*; D015398:Signal Transduction / Q000502:physiology; D023001:Transplantation Tolerance / Q000502:physiology
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase