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Myocardial inflammatory activation in children with congenital heart disease
Steven S Mou1, Sandra B Haudek, Laurance Lequier
1Department of Pediatrics, University of Texas Southwestern Medical School, Dallas, TX, USA.
Insights
This study found that 60% of children with congenital heart disease showed signs of myocardial inflammation, indicated by nuclear factor-kappaB activation, even before heart surgery. These findings suggest inflammation plays a role in pediatric heart disease.
Area of Science:
- Pediatric Cardiology
- Molecular Biology
- Immunology
Background:
- Systemic endotoxemia and myocardial cytokine production are linked to cardiac failure in various heart diseases.
- Previous studies indicated pre- and postoperative endotoxemia in children with congenital heart disease (CHD).
Purpose of the Study:
- To investigate direct evidence of myocardial inflammatory activation in children undergoing congenital heart surgery.
- To define inflammatory activation by assessing nuclear factor-kappaB (NF-κB) nuclear translocation in myocardial tissue.
Main Methods:
- Prospective observational study in a pediatric intensive care unit.
- Fifteen children with CHD undergoing cardiopulmonary bypass (CPB) surgery were included.
- Plasma samples for endotoxin and tumor necrosis factor-alpha (TNF-α) were collected pre- and postoperatively.
- Myocardial tissue samples were obtained intraoperatively before and during CPB.
Main Results:
- All 15 patients had elevated plasma endotoxin levels; 12 showed elevation before CPB.
- Median preoperative TNF-α levels were higher than in adults with advanced heart failure.
- Nuclear factor-kappaB (NF-κB) nuclear translocation was observed in 60% of myocardial samples.
- NF-κB translocation occurred preoperatively in 4 patients, with specific dimer formations noted.
Conclusions:
- This study provides the first evidence of NF-κB activation in children with CHD.
- It is the first demonstration of myocardial NF-κB translocation in human hearts prior to transplantation.
- The findings suggest that myocardial inflammation contributes to the pathophysiology of pediatric CHD, similar to adult heart failure.
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.