title: Real-time monitoring of liver damage during experimental ischaemia-reperfusion using a nitric oxide sensor.
abstract: BACKGROUND
  Hepatic ischaemia-reperfusion (IR) injury may lead to liver damage during liver surgery, and intrahepatic nitric oxide (NO) levels may play a role in this context. The aim of this study was to demonstrate real-time changes in intrahepatic NO concentration during IR and to correlate potential hepatic NO production with liver damage using a selective NO sensor.
  
  
  METHODS
  Wistar rats were exposed to 15 min of hepatic ischaemia followed by reperfusion, after which changes in intrahepatic NO levels were measured using an NO sensor. Additionally, rats were exposed to five successive periods of IR, each consisting of 15 min ischaemia followed by 5 or 15 min reperfusion, and hepatic damage was evaluated by blood tests and histological examination. Hepatic expression of Akt, phosphorylated Akt, endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS was examined at different time points during and after IR by western blot and immunohistochemical analysis.
  
  
  RESULTS
  During ischaemia, intrahepatic NO levels increased and reached a plateau at approximately 10 min. Repeated 15 min ischaemia-5 min reperfusion cycles reduced the maximum amount of NO produced during ischaemia gradually, and almost no NO production was observed during the fifth period of ischaemia. NO production following repeated ischaemia was proportional to the degree of hepatic viability. Phosphorylated eNOS was upregulated and correlated with the level of NO production during hepatic ischaemia.
  
  
  CONCLUSIONS
  Intrahepatic NO levels decrease during repeated IR in rats. Real-time monitoring of intrahepatic NO levels is useful for the prediction of IR-related liver injury during experimental liver surgery.
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Nakagawa
authors.forename: Y
authors.initials: Y
authors.lastname: Yokoyama
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
authors.forename: K
authors.initials: K
authors.lastname: Shoji
authors.forename: Y
authors.initials: Y
authors.lastname: Watanabe
authors.forename: A
authors.initials: A
authors.lastname: Imamura
authors.forename: T
authors.initials: T
authors.lastname: Kokuryo
authors.forename: M
authors.initials: M
authors.lastname: Nagino
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003250:Constriction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry; D007511:Ischemia / Q000378:metabolism*; D008099:Liver / Q000098:blood supply*; D008239:Lysine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000175:diagnosis*
chemical_list: D004791:Enzyme Inhibitors; C090663:N(6)-(1-iminoethyl)lysine; D052250:Nitric Oxide Synthase Type III; D008239:Lysine; D019331:NG-Nitroarginine Methyl Ester