Myocardial inflammatory activation in children with congenital heart disease

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. DESIGN: Prospective observational study. SETTING: Tertiary care pediatric intensive care unit. PATIENTS: Fifteen children with congenital heart disease undergoing operative repair on cardiopulmonary bypass. INTERVENTIONS: 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. MEASUREMENTS AND MAIN 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.