Elevated immunoreactive endothelin-1 levels in newborn infants with persistent pulmonary hypertension

Abstract

To study the potential role of endothelin-1, a potent endothelium-derived vasoconstrictor peptide, in the pathophysiology of persistent pulmonary hypertension of the newborn (PPHN), we measured arterial concentrations of immunoreactive endothelin-1 (irET-1) in 24 neonates with PPHN. Secondary diagnoses included meconium aspiration syndrome (13 patients), sepsis (2), congenital diaphragmatic hernia (1), asphyxia (1), pulmonary hemorrhage (1), aspiration of blood (1), and respiratory distress syndrome (1). Compared with irET-1 levels in umbilical cord blood in normal infants (15.1 +/- 4.1 pg/ml; mean +/- SEM) and in newborn infants with hyaline membrane disease who were supported by mechanical ventilation (11.8 +/- 1.2 pg/ml), infants with PPHN had markedly elevated circulating irET-1 levels (27.6 +/- 3.6 pg/ml; p < 0.01 vs cord blood, hyaline membrane disease). Infants with severe PPHN requiring extracorporeal membrane oxygenation (ECMO) therapy had higher irET-1 levels than infants with milder disease (31.0 +/- 4.7 for ECMO-treated infants vs 21.2 +/- 2.0 for non-ECMO-treated infants; p < 0.05). In patients treated without ECMO, irET-1 progressively decreased during the following 3 to 5 days, paralleling clinical improvement. In contrast, irET-1 concentrations remained elevated in infants with severe PPHN during ECMO therapy. We conclude that circulating irET-1 levels are elevated in newborn infants with PPHN, are positively correlated with disease severity, and decline with resolution of disease in patients who do not require ECMO therapy. Whether endothelin-1 contributes directly to the pathophysiology of PPHN or is simply a marker of disease activity remains speculative.