title: Ischemic preconditioning protects the steatotic mouse liver against reperfusion injury: an ATP dependent mechanism.
abstract: OBJECTIVE
  Hepatic steatosis is a major risk factor for liver surgery and transplantation. The increased susceptibility of fatty livers to ischemic injury is associated with a necrotic form of cell death as opposed to apoptosis in lean animals, and is possibly related to low contents of ATP. Ischemic preconditioning, a brief period of ischemia prior to a prolonged period, protects the lean liver against ischemia through anti-apoptotic properties. We evaluated whether ischemic preconditioning also confers protection in the fatty liver and whether it protects against the ATP loss.
  
  
  METHODS
  The effect of ischemic preconditioning was tested in steatotic and lean livers subjected to 75 min of ischemia and 4 or 24 h of reperfusion. Tissue ATP contents were assessed at various times, and a model of low hepatic ATP contents (starvation) was studied to assess the type of injury following ischemia and the effects of preconditioning.
  
  
  RESULTS
  Ischemic preconditioning protected steatotic livers against massive necrosis. ATP levels were significantly higher before and after reperfusion in liver subjected to preconditioning when compared to controls. Liver with low baseline ATP levels (starvation) were also associated with necrosis, and were protected by ischemic preconditioning.
  
  
  CONCLUSIONS
  Ischemic preconditioning mainly protects the fatty liver against necrosis possibly through preservation and restoration of tissue ATP contents.
authors.affiliation: Laboratory of Liver Transplantation and Hepatobiliary Surgery, Department of Visceral Surgery and Transplantation, University of Zurich, Rämistrasse 100, 8091 Zurich, Switzerland.
authors.forename: Nazia
authors.initials: N
authors.lastname: Selzner
authors.forename: Markus
authors.initials: M
authors.lastname: Selzner
authors.forename: Wolfram
authors.initials: W
authors.lastname: Jochum
authors.forename: Pierre-Alain
authors.initials: PA
authors.lastname: Clavien
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D005234:Fatty Liver / Q000378:metabolism* / Q000473:pathology; D019194:Ischemic Preconditioning; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control
chemical_list: D000255:Adenosine Triphosphate