title: Efferent vagal nerve stimulation attenuates acute lung injury following burn: The importance of the gut-lung axis.
abstract: BACKGROUND
  The purpose of this study was to assess acute lung injury when protection to the gut mucosal barrier offered by vagus nerve stimulation is eliminated by an abdominal vagotomy.
  
  
  METHODS
  Male balb/c mice were subjected to 30% total body surface area steam burn with and without electrical stimulation to the right cervical vagus nerve. A cohort of animals were subjected to abdominal vagotomy. Lung histology, myeloperoxidase and ICAM-1 immune staining, myeloperoxidase enzymatic assay, and tissue KC levels were analyzed 24 hours after burn. Additionally, lung IkB-α, NF-kB immunoblots, and NF-kB-DNA binding measured by photon emission analysis using NF-kB-luc transgenic mice were performed.
  
  
  RESULTS
  Six hours post burn, phosphorylation of both NF-kB p65 and IkB-α were observed. Increased photon emission signal was seen in the lungs of NF-kB-luc transgenic animals. Vagal nerve stimulation blunted NF-kB activation similar to sham animals whereas abdominal vagotomy eliminated the anti-inflammatory effect. After burn, MPO positive cells and ICAM-1 expression in the lung endothelium was increased, and lung histology demonstrated significant injury at 24 hours. Vagal nerve stimulation markedly decreased neutrophil infiltration as demonstrated by MPO immune staining and enzyme activity. Vagal stimulation also markedly attenuated acute lung injury at 24 hours. The protective effects of vagal nerve stimulation were reversed by performing an abdominal vagotomy.
  
  
  CONCLUSIONS
  Vagal nerve stimulation is an effective strategy to protect against acute lung injury following burn. Moreover, the protective effects of vagal nerve stimulation in the prevention of acute lung injury are eliminated by performing an abdominal vagotomy. These results establish the importance of the gut-lung axis after burn in the genesis of acute lung injury.
authors.affiliation: Division of Trauma, Surgical Critical Care, and Burns, Department of Surgery, University of California, San Diego School of Medicine, San Diego, CA, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Krzyzaniak
authors.forename: Carrie Y
authors.initials: CY
authors.lastname: Peterson
authors.forename: Gerald
authors.initials: G
authors.lastname: Cheadle
authors.forename: William
authors.initials: W
authors.lastname: Loomis
authors.forename: Paul
authors.initials: P
authors.lastname: Wolf
authors.forename: Vince
authors.initials: V
authors.lastname: Kennedy
authors.forename: James G
authors.initials: JG
authors.lastname: Putnam
authors.forename: Vishal
authors.initials: V
authors.lastname: Bansal
authors.forename: Brian
authors.initials: B
authors.lastname: Eliceiri
authors.forename: Andrew
authors.initials: A
authors.lastname: Baird
authors.forename: Raul
authors.initials: R
authors.lastname: Coimbra
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control*; D000818:Animals; D001707:Biopsy, Needle; D002056:Burns / Q000150:complications* / Q000175:diagnosis; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D041981:Gastrointestinal Tract / Q000473:pathology*; D015151:Immunoblotting; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009195:Peroxidase / Q000378:metabolism; D011897:Random Allocation; D012016:Reference Values; D016896:Treatment Outcome; D014628:Vagotomy / Q000379:methods; D055536:Vagus Nerve Stimulation / Q000379:methods*
chemical_list: D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase