title: Intestinal injury and endotoxemia in children undergoing surgery for congenital heart disease.
abstract: BACKGROUND
  Children with congenital heart disease are at risk of gut barrier dysfunction and translocation of gut bacterial antigens into the bloodstream. This may contribute to inflammatory activation and organ dysfunction postoperatively.
  
  
  OBJECTIVE
  To investigate the role of intestinal injury and endotoxemia in the pathogenesis of organ dysfunction after surgery for congenital heart disease.
  
  
  METHODS
  We analyzed blood levels of intestinal fatty acid binding protein and endotoxin (endotoxin activity assay) alongside global transcriptomic profiling and assays of monocyte endotoxin receptor expression in children undergoing surgery for congenital heart disease.
  
  
  RESULTS
  Levels of intestinal fatty acid binding protein and endotoxin were greater in children with duct-dependent cardiac lesions. Endotoxemia was associated with severity of vital organ dysfunction and intensive care stay. We identified activation of pathogen-sensing, antigen-processing, and immune-suppressing pathways at the genomic level postoperatively and down-regulation of pathogen-sensing receptors on circulating immune cells.
  
  
  CONCLUSIONS
  Children undergoing surgery for congenital heart disease are at increased risk of intestinal mucosal injury and endotoxemia. Endotoxin activity correlates with a number of outcome variables in this population, and may be used to guide the use of gut-protective strategies.
authors.affiliation: Department of Paediatrics, Imperial College London, London, England, UK. n.pathan@imperial.ac.uk
authors.forename: Nazima
authors.initials: N
authors.lastname: Pathan
authors.forename: Margarita
authors.initials: M
authors.lastname: Burmester
authors.forename: Tanja
authors.initials: T
authors.lastname: Adamovic
authors.forename: Maurice
authors.initials: M
authors.lastname: Berk
authors.forename: Keng Wooi
authors.initials: KW
authors.lastname: Ng
authors.forename: Helen
authors.initials: H
authors.lastname: Betts
authors.forename: Duncan
authors.initials: D
authors.lastname: Macrae
authors.forename: Simon
authors.initials: S
authors.lastname: Waddell
authors.forename: Mark
authors.initials: M
authors.lastname: Paul-Clark
authors.forename: Rosamund
authors.initials: R
authors.lastname: Nuamah
authors.forename: Charles
authors.initials: C
authors.lastname: Mein
authors.forename: Michael
authors.initials: M
authors.lastname: Levin
authors.forename: Giovanni
authors.initials: G
authors.lastname: Montana
authors.forename: Jane A
authors.initials: JA
authors.lastname: Mitchell
mesh_terms: D015536:Down-Regulation / Q000276:immunology; D019446:Endotoxemia / Q000097:blood / Q000276:immunology / Q000382:microbiology*; D004797:Enzyme-Linked Immunosorbent Assay; D050556:Fatty Acid-Binding Proteins / Q000097:blood / Q000276:immunology; D005260:Female; D006330:Heart Defects, Congenital / Q000601:surgery*; D006801:Humans; D007223:Infant; D007249:Inflammation / Q000097:blood / Q000276:immunology / Q000382:microbiology; D007410:Intestinal Diseases / Q000097:blood / Q000276:immunology / Q000382:microbiology*; D007413:Intestinal Mucosa / Q000276:immunology / Q000293:injuries* / Q000382:microbiology*; D007902:Length of Stay / Q000706:statistics & numerical data; D008297:Male; D009102:Multiple Organ Failure / Q000097:blood / Q000276:immunology / Q000382:microbiology; D011183:Postoperative Complications / Q000097:blood / Q000276:immunology / Q000382:microbiology; D012720:Severity of Illness Index
chemical_list: D050556:Fatty Acid-Binding Proteins