title: Ischemic preconditioning protects from hepatic ischemia/reperfusion-injury by preservation of microcirculation and mitochondrial redox-state.
abstract: OBJECTIVE
  Ischemic preconditioning (IP) is known to protect hepatic tissue from ischemia-reperfusion injury. However, the mechanisms involved are not fully understood yet.
  
  
  METHODS
  Using intravital multifluorescence microscopy in the rat liver, we studied whether IP exerts its beneficial effect by modulating postischemic Kupffer cell activation, leukocyte-endothelial cell interaction, microvascular no-reflow, mitochondrial redox state, and, thus, tissue oxygenation.
  
  
  RESULTS
  Portal triad cross-clamping (45 min) followed by reperfusion induced Kupffer cell activation, microvascular leukocyte adherence, sinusoidal perfusion failure (no-reflow) and alteration of mitochondrial redox state (tissue hypoxia) (P<0.05). This resulted in liver dysfunction and parenchymal injury, as indicated by decreased bile flow and increased serum glutamate dehydrogenase (GLDH) levels (P<0.05). IP (5 min ischemia and 30 min intermittent reperfusion) was capable to significantly reduce Kupffer cell activation (P<0.05), which was associated with a slight attenuation of leukocyte adherence. Further, IP markedly ameliorated sinusoidal perfusion failure (P<0.05), and, thereby, preserved adequate mitochondrial redox state (P<0.05). As a consequence, IP prevented the decrease of bile flow (P<0.05) and the increase in serum GLDH levels (P<0.05).
  
  
  CONCLUSIONS
  IP may exert its beneficial effects on hepatic ischemia-reperfusion injury by preserving mitochondrial redox state, which is guaranteed by the prevention of reperfusion-associated Kupffer cell activation and sinusoidal perfusion failure.
authors.affiliation: Department of General, Visceral and Transplantation Surgery, Charité, Campus Virchow Klinikum, Humboldt University Berlin, Berlin, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Glanemann
authors.forename: Brigitte
authors.initials: B
authors.lastname: Vollmar
authors.forename: Andreas K
authors.initials: AK
authors.lastname: Nussler
authors.forename: Thilo
authors.initials: T
authors.lastname: Schaefer
authors.forename: Peter
authors.initials: P
authors.lastname: Neuhaus
authors.forename: Michael D
authors.initials: MD
authors.lastname: Menger
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D019194:Ischemic Preconditioning; D007728:Kupffer Cells / Q000502:physiology; D007962:Leukocytes / Q000502:physiology; D008099:Liver / Q000378:metabolism / Q000502:physiology; D008102:Liver Circulation; D008297:Male; D008833:Microcirculation; D008930:Mitochondria, Liver / Q000378:metabolism*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D010587:Phagocytosis; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*
chemical_list: D010100:Oxygen