title: Myocardial inflammatory activation in children with congenital heart disease.
abstract: OBJECTIVE
  In several cardiac-related diseases, there is a strong association between systemic endotoxemia, myocardial cytokine production, and cardiac failure. Because pre- and postoperative endotoxemia recently was reported in children with congenital heart disease, we sought direct evidence of myocardial inflammatory activation in a cohort of children undergoing congenital heart surgery on cardiopulmonary bypass. Inflammatory activation was prospectively defined as the presence of nuclear factor-kappaB nuclear translocation in myocardial tissue samples.
  
  
  METHODS
  Prospective observational study.
  
  
  METHODS
  Tertiary care pediatric intensive care unit.
  
  
  METHODS
  Fifteen children with congenital heart disease undergoing operative repair on cardiopulmonary bypass.
  
  
  METHODS
  All patients underwent operative repair of congenital heart disease on cardiopulmonary bypass and had plasma samples obtained for endotoxin and tumor necrosis factor-alpha, both pre- and postoperatively. Myocardial tissue samples were obtained intraoperatively, both before and during cardiopulmonary bypass.
  
  
  RESULTS
  Elevated plasma endotoxin concentrations were documented in all 15 patients during the study period. In 12 patients, plasma endotoxin was elevated before cardiopulmonary bypass. The median preoperative tumor necrosis factor-alpha concentration was 16.4 pg/mL, which is higher than concentrations reported in adults with New York Heart Association class III congestive heart failure. Examination of myocardial tissue samples revealed nuclear factor-kappaB nuclear translocation (predominantly p50/p65 heterodimers) in nine of 15 patients (60%). Four of these nine patients had nuclear factor-kappaB nuclear translocation before initiation of cardiopulmonary bypass, with p50/p50 homodimers present in two of the four.
  
  
  CONCLUSIONS
  These data provide the first evidence of nuclear factor-kappaB activation in children with congenital heart disease and the first evidence of myocardial nuclear factor-kappaB translocation in human hearts before explant for transplantation. Furthermore, these data suggest that, similar to adults with advanced congestive heart failure, the myocardial inflammatory cascade may contribute to the pathophysiology of congenital heart disease in infants and children.
authors.affiliation: Department of Pediatrics, University of Texas Southwestern Medical School, Dallas, TX, USA.
authors.forename: Steven S
authors.initials: SS
authors.lastname: Mou
authors.forename: Sandra B
authors.initials: SB
authors.lastname: Haudek
authors.forename: Laurance
authors.initials: L
authors.lastname: Lequier
authors.forename: Olivia
authors.initials: O
authors.lastname: Peña
authors.forename: Steven
authors.initials: S
authors.lastname: Leonard
authors.forename: Hisashi
authors.initials: H
authors.lastname: Nikaidoh
authors.forename: Brett P
authors.initials: BP
authors.lastname: Giroir
authors.forename: Daniel
authors.initials: D
authors.lastname: Stromberg
mesh_terms: D021581:Active Transport, Cell Nucleus; D000328:Adult; D002315:Cardiopulmonary Bypass; D002675:Child, Preschool; D004731:Endotoxins / Q000097:blood; D005260:Female; D006330:Heart Defects, Congenital / Q000276:immunology* / Q000601:surgery; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007249:Inflammation / Q000209:etiology; D008297:Male; D009206:Myocardium / Q000276:immunology*; D016328:NF-kappa B / Q000032:analysis*; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D004731:Endotoxins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha