title: Neural elements behind the hepatoprotection of remote perconditioning.
abstract: BACKGROUND
  The ability of remote ischemic perconditioning (RIPER) to protect the liver from ischemic-reperfusion (IR) injury has been reported before; however, the mechanism behind the positive effects of RIPER remains unrevealed. Therefore, we aimed to investigate the potential role of neural elements to transfer protective signals evoked by perconditioning.
  
  
  METHODS
  Male Wistar rats were randomly allocated into six groups (sham, IR, RIPER ± denervation; n = 7 per group). Half of the animals underwent left femoral and sciatic nerve resection. In IR and RIPER groups, normothermic, partial (70%) liver ischemia lasting for 60 min was induced; parallel animals in the RIPER groups received perconditioning treatment (4 × 5 - 5 min IR, left femoral artery clamping). Hepatic microcirculation and systemic blood pressure were monitored during the first postischemic hour. After 24 h of reperfusion, liver samples were taken for histology and redox-state analysis. Automated image analysis software was used for necrosis quantification. Serum alanine aminotransferase, aspartate aminotransferase, and bilirubin levels were measured.
  
  
  RESULTS
  Microcirculation and blood pressure showed significant improvement during reperfusion after perconditioning. This phenomenon was completely abolished by nerve resection (P < 0.05; RIPER versus IR, IR + denervation, and RIPER + denervation). Results of necrosis quantification showed similar pattern. Besides noncharacteristic changes in aspartate aminotransferase levels, alanine aminotransferase values were significantly lower (P < 0.05) in the RIPER group compared with the other IR groups. Mild but significant alterations were observed in liver function assessed by total bilirubin levels. Further supporting results were obtained from analysis of redox homeostasis.
  
  
  CONCLUSIONS
  Perconditioning was able to reduce liver IR injury in our model via a mechanism most probably involving interorgan neural pathways.
authors.affiliation: 1st Department of Surgery, Semmelweis University, Budapest, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Czigány
authors.affiliation: 1st Department of Surgery, Semmelweis University, Budapest, Hungary.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Turóczi
authors.affiliation: Institute of Pharmacognosy, Semmelweis University, Budapest, Hungary.
authors.forename: Dénes
authors.initials: D
authors.lastname: Kleiner
authors.affiliation: 2nd Department of Pathology, Semmelweis University, Budapest, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Lotz
authors.affiliation: Fraunhofer MEVIS, Institute for Medical Image Computing, Bremen, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Homeyer
authors.affiliation: 1st Department of Surgery, Semmelweis University, Budapest, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Harsányi
authors.affiliation: 1st Department of Surgery, Semmelweis University, Budapest, Hungary. Electronic address: szijartoattila@gmail.com.
authors.forename: Attila
authors.initials: A
authors.lastname: Szijártó
mesh_terms: D000818:Animals; D005263:Femoral Artery; D005267:Femoral Nerve / Q000502:physiology / Q000601:surgery; D019194:Ischemic Preconditioning; D008099:Liver / Q000098:blood supply; D008107:Liver Diseases / Q000517:prevention & control*; D035002:Lower Extremity / Q000098:blood supply / Q000294:innervation*; D008297:Male; D008833:Microcirculation; D010084:Oxidation-Reduction; D011897:Random Allocation; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*; D012584:Sciatic Nerve / Q000502:physiology / Q000601:surgery
keywords: Histologic image analysis; Ischemia; Liver diseases; Microcirculation; Remote perconditioning; Reperfusion injury