title: Continuous infusion of N-acetylcysteine reduces liver warm ischaemia-reperfusion injury.
abstract: BACKGROUND
  N-acetylcysteine (NAC) may modulate the initial phase (less than 2 h) of liver warm ischaemia-reperfusion (IR) injury but its effect on the late phase remains unclear. The present study investigated the role of NAC during the early and late phases in a rabbit lobar IR model.
  
  
  METHODS
  Liver ischaemia was induced by inflow occlusion to the median and left liver lobes for 60 min, followed by 7 h of reperfusion. In the NAC group (n = 6), NAC was administered intravenously at 150 mg per kg over the 15 min before reperfusion and maintained at 10 mg per kg per h during reperfusion. In the IR group (n = 6), 20 ml 5 per cent dextrose was infused over the 15 min before reperfusion and continued at a rate of 10 ml/h. Animals in a sham operation group (n = 6) underwent laparotomy but no liver ischaemia. All animals were killed at the end of the experiment.
  
  
  RESULTS
  Intracellular tissue oxygenation was improved after the second hour of reperfusion in animals treated with NAC compared with that in the IR group (P = 0.023). Hepatic microcirculation improved after 5 h of reperfusion (P = 0.036) and liver injury was reduced after 5 h, as indicated by alanine aminotransferase activity (P = 0.007) and indocyanine green clearance (uptake, P = 0.001; excretion, P = 0.032).
  
  
  CONCLUSIONS
  The main protective effect of NAC becomes apparent 5 h after hepatic ischaemic injury.
authors.affiliation: Hepatopancreaticobiliary and Liver Transplant Unit, University Department of Surgery, Royal Free and University College School of Medicine, University College London and Royal Free Hospital NHS Trust, London, UK.
authors.forename: G K
authors.initials: GK
authors.lastname: Glantzounis
authors.forename: W
authors.initials: W
authors.lastname: Yang
authors.forename: R S
authors.initials: RS
authors.lastname: Koti
authors.forename: D P
authors.initials: DP
authors.lastname: Mikhailidis
authors.forename: A M
authors.initials: AM
authors.lastname: Seifalian
authors.forename: B R
authors.initials: BR
authors.lastname: Davidson
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage*; D000818:Animals; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D007208:Indocyanine Green / Q000493:pharmacokinetics; D019194:Ischemic Preconditioning / Q000379:methods; D008099:Liver / Q000098:blood supply*; D008102:Liver Circulation; D008111:Liver Function Tests; D008833:Microcirculation; D011817:Rabbits; D015427:Reperfusion Injury / Q000517:prevention & control*
chemical_list: D016166:Free Radical Scavengers; D007208:Indocyanine Green; D000111:Acetylcysteine