Endogenous nitric oxide and soluble tumor necrosis factor receptor levels are enhanced in infants with congenital heart disease

OBJECTIVE This study was designed to investigate cytokine and nitric oxide levels in pediatric patients suffering from chronic heart failure and to investigate effects of β-blocker treatment on these levels. PATIENTS Fifteen infants with heart failure resulting from left-to-right shunts with pulmonary overcirculation were compared with 11 infants with cyanotic heart defects with reduced pulmonary blood flow. Four of these patients were finally treated with the β-blocker propranolol. MEASUREMENTS Endogenous nitric oxide production was determined by measuring total plasma nitrite/nitrate (Griess method), and levels of soluble tumor necrosis factor receptors type 1 and type 2 (TNF-R1 and TNF-R2, respectively) were measured by commercially available enzyme-linked immunosorbent assay. MAIN RESULTS In infants with left-to-right shunts, soluble tumor necrosis factor receptor levels were significantly elevated as compared with infants with cyanosis (TNF-R11.7 ± 0.5 vs. 0.8 ± 0.3 ng/mL;p = .0003; TNF-R28.1 ± 4.0 vs. 5.1 ± 3.2 ng/mL;p = .049). In addition, we found a significant correlation between nitrate/nitrite levels and TNF-R1 (r = .70;p = .0001) or TNF-R2 (r = .62;p = .0013), respectively. Furthermore, the tumor necrosis factor receptor levels in four children after β-blocker treatment were lower as compared with levels before β-blocker treatment. CONCLUSIONS Immune mechanisms, such as cytokine or nitric oxide production, may be involved in pathogenesis of heart failure in children, and may contribute to the beneficial effects of β-blocker treatment observed in these patients.