title: Tumor necrosis factor suppression and microcirculatory disturbance amelioration in ischemia/reperfusion injury of rat liver after ischemic preconditioning.
abstract: BACKGROUND
  Brief periods of hepatic ischemia produce immediate tolerance for subsequent prolonged ischemia. Although the beneficial effect of this ischemic preconditioning is recognized, the mechanism itself remains poorly understood.
  
  
  METHODS
  Male Wistar rats were divided into two groups: a control group that was subjected to 30 min of ischemia + following reperfusion, and an ischemic preconditioning group that was subjected to 5 min of ischemia + 5 min of reperfusion + 30 min of ischemia + following reperfusion. By using this model, hepatic damage, microcirculatory disturbances, and tumor necrosis factor-alpha protein production and mRNA expression were analyzed during the course of reperfusion in both groups. For the hepatic damage evaluations, hepatic enzyme levels, histology, apoptosis analysis, and intravital microfluorography for dead cells were examined. For the microcirculatory disturbance analysis, an adhesion molecule and intravital microfluorography for endothelial-adherent leukocytes were examined.
  
  
  RESULTS
  In the ischemic preconditioning group, ischemia/reperfusion injuries (shown by hepatic enzymes elevation, histological degeneration, and increases in the number of apoptotic cells and microfluorographic dead cells) were markedly reduced. Moreover, microcirculatory disturbances represented by intercellular adhesion molecule-1 expression and leukocyte adhesion on the endothelium were ameliorated. Tumor necrosis factor-alpha protein production and mRNA expression were also suppressed in the ischemic preconditioning group.
  
  
  CONCLUSIONS
  The suppression of tumor necrosis factor-alpha and the subsequent amelioration of microcirculatory disturbances were observed, suggesting that the mechanism underlying the protective effect of ischemic preconditioning in hepatic ischemia/reperfusion injuries may involve tumor necrosis factor-alpha and microcirculatory regulation.
authors.affiliation: Department of Surgery, Keio University School of Medicine, Tokyo, Japan. masahiro@sc.itc.keio.ac.jp
authors.forename: Masahiro
authors.initials: M
authors.lastname: Shinoda
authors.forename: Motohide
authors.initials: M
authors.lastname: Shimazu
authors.forename: Go
authors.initials: G
authors.lastname: Wakabayashi
authors.forename: Minoru
authors.initials: M
authors.lastname: Tanabe
authors.forename: Ken
authors.initials: K
authors.lastname: Hoshino
authors.forename: Masaki
authors.initials: M
authors.lastname: Kitajima
mesh_terms: D000818:Animals; D017209:Apoptosis; D020287:In Situ Nick-End Labeling; D007511:Ischemia / Q000503:physiopathology*; D019194:Ischemic Preconditioning; D008099:Liver / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D008102:Liver Circulation / Q000502:physiology; D008111:Liver Function Tests; D008297:Male; D008833:Microcirculation; D008856:Microscopy, Fluorescence; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha