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 i nvestigate effects of beta -blocker treatment on these levels. Patients: Fifteen infants with heart failure resulting from left-to-right s hunts with pulmonary overcirculation were compared with 11 infants with cya notic heart defects with reduced pulmonary blood flow. Four of these patien ts were finally treated with the beta -blocker propranolol. Measurements. Endogenous nitric oxide production was determined by measurin g total plasma nitrite/nitrate (Griess method), and levels of soluble tumor necrosis factor receptors type 1 and type 2 (TNF-R1 and TNF-R2, respective ly) were measured by commercially available enzyme-linked immunosorbent ass ay. 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-R1: 1.7 +/- 0.5 vs. 0.8 +/- 0.3 ng/mL; p = .0003; TNF-R 2: 8.1 +/- 4.0 vs. 5.1 +/- 3.2 ng/mL; p = .049). In addition, we found a si gnificant correlation between nitrate/nitrite levels and TNF-R1 (r = .70; p = .0001) or TNF-R2 (r = .62; p = .0013), respectively. Furthermore, the tu mor necrosis factor receptor levels in four children after beta -blocker tr eatment were lower as compared with levels before beta -blocker treatment. Conclusions: Immune mechanisms, such as cytokine or nitric oxide production , may be involved in pathogenesis of heart failure in children, and may con tribute to the beneficial effects of beta -blocker treatment observed in th ese patients.