Chronic Hypoxemia in Children With Congenital Heart Defect Impairs Airway Epithelial Sodium Transport.

Objective: Ambient hypoxia impairs the airway epithelial Na+ transport, which is crucial in lung edema reabsorption. Whether chronic systemic hypoxemia affects airway Na+ transport has remained largely unknown. We have therefore investigated whether chronic systemic hypoxemia in children with congenital heart defect affects airway epithelial Na+ transport, Na+ transporter-gene expression, and short-term lung edema accumulation. Design: Prospective, observational study. Setting: Tertiary care medical center responsible for nationwide pediatric cardiac surgery. Patients: Ninety-nine children with congenital heart defect or acquired heart disease (age range, 6 d to 14.8 yr) were divided into three groups based on their level of preoperative systemic hypoxemia: 1) normoxemic patients (Spo(2)% 95%; n = 44), 2) patients with cyanotic congenital heart defect and moderate hypoxemia (Spo(2) 86-94%; n = 16), and 3) patients with cyanotic congenital heart defect and profound systemic hypoxemia (Spo(2) 85%; n = 39). Measurements and Main Results: Nasal transepithelial potential difference served as a surrogate measure for epithelial Na+ transport of the respiratory tract. Profoundly hypoxemic patients had 29% lower basal nasal transepithelial potential difference (p = 0.02) and 55% lower amiloride-sensitive nasal transepithelial potential difference (p = 0.0003) than normoxemic patients. In profoundly hypoxemic patients, nasal epithelial messenger RNA expressions of two airway Na+ transporters (amiloride-sensitive epithelial Na+ channel and 1- Na-K-ATPase) were not attenuated, but instead 1-Na-K-ATPase messenger RNA levels were higher (p = 0.03) than in the normoxemic patients, indicating that posttranscriptional factors may impair airway Na+ transport. The chest radiograph lung edema score increased after congenital cardiac surgery in profoundly hypoxemic patients (p = 0.0004) but not in patients with normoxemia or moderate hypoxemia. Conclusions: The impaired airway epithelial amiloride-sensitive Na+ transport activity in profoundly hypoxemic children with cyanotic congenital heart defect may hinder defense against lung edema after cardiac surgery.