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 beta-blocker treatment on these levels.


METHODS
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 beta-blocker propranolol.


METHODS
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.


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-R2: 8.1 +/- 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 beta-blocker treatment 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 contribute to the beneficial effects of beta-blocker treatment observed in these patients.
Buchhorn
R
R
Department of Pediatric Cardiology, Georg-August-University Göttingen, Göttingen, Germany. rbuchho@gwdg.de
Wessel
A
A
Hulpke-Wette
M
M
Bürsch
J
J
Werdan
K
K
Loppnow
H
H
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D006330:Heart Defects, Congenital / Q000378:metabolism*; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D009569:Nitric Oxide / Q000097:blood*; D011433:Propranolol / Q000627:therapeutic use*; D011652:Pulmonary Circulation / Q000187:drug effects; D018124:Receptors, Tumor Necrosis Factor / Q000302:isolation & purification / Q000378:metabolism*
D000319:Adrenergic beta-Antagonists; D018124:Receptors, Tumor Necrosis Factor; D009569:Nitric Oxide; D011433:Propranolol