Inhaled NO improves early pulmonary function and modifies lung growth and elastin deposition in a baboon model of neonatal chronic lung disease

TLDR

Nitric oxide (NO) plays multiple roles in lung development, yet pulmonary NO production is reduced in a baboon model of chronic lung disease after premature birth at 125 days gestation. The study aimed to determine whether postnatal inhaled NO (iNO, 5 ppm) alters the genesis of chronic lung disease in this baboon model. The authors assessed the effects of iNO over a 14‑day period in the baboon model. In this model, iNO lowered pulmonary artery pressure, accelerated ductus arteriosus closure, improved lung compliance and expiratory resistance, shifted pressure‑volume curves upward, increased lung DNA content and cell proliferation, preserved lung growth, normalized excessive elastin deposition, stimulated secondary crest development, and overall improved early pulmonary function and altered lung growth and extracellular matrix deposition, suggesting that NO biosynthetic pathway dysfunction may contribute to chronic lung disease pathogenesis.

Abstract

Nitric oxide (NO) serves multiple functions in the developing lung, and pulmonary NO production is decreased in a baboon model of chronic lung disease (CLD) after premature birth at 125 days (d) gestation (term = 185d). To determine whether postnatal NO administration alters the genesis of CLD, the effects of inhaled NO (iNO, 5 ppm) were assessed in the baboon model over 14d. iNO caused a decrease in pulmonary artery pressure in the first 2d and a greater rate of spontaneous closure of the ductus arteriosus, and lung compliance was greater and expiratory resistance was improved during the first week. With iNO, postmortem pressure-volume curves were shifted upward, lung DNA content and cell proliferation were increased, and lung growth was preserved to equal that which occurs during the same period in utero. In addition, the excessive elastin deposition characteristic of CLD was normalized by iNO, and there was evidence of stimulation of secondary crest development. Thus, in the baboon model of CLD, iNO improves early pulmonary function and alters lung growth and extracellular matrix deposition. As such, NO biosynthetic pathway dysfunction may contribute to the pathogenesis of CLD.