Effects of inhaled nitric oxide on pulmonary edema and lung neutrophil accumulation in severe experimental hyaline membrane disease

Pediatr Res. 1997 Apr;41(4 Pt 1):457-63. doi: 10.1203/00006450-199704000-00002.


To determine the effects of inhaled NO (iNO) on pulmonary edema and lung inflammation in experimental hyaline membrane disease (HMD), we measured the effects of iNO on pulmonary hemodynamics, gas exchange, pulmonary edema, and lung myeloperoxidase (MPO) activity in extremely premature lambs (115 d of gestation, 0.78 term). In protocol 1, we measured the effects of iNO (20 ppm) on lung vascular endothelial permeability to 125I-labeled albumin (indexed to blood volume using 57Cr-tagged red blood cells) during 1 h (n = 10) and 3 h (n = 14) of conventional mechanical ventilation with FiO2 = 1.00. In comparison with controls, iNO improved pulmonary hemodynamics and gas exchange, but did not alter lung weight-to-dry weight ratio or vascular permeability to albumin after 1 or 3 h of mechanical ventilation. To determine whether low dose iNO (5 ppm) would decrease lung neutrophil accumulation in severe HMD, we measured lung MPO activity after 4 h of mechanical ventilation with or without iNO (protocol 2). Low dose iNO improved gas exchange during 4 h of mechanical ventilation (PaO2 at 4 h: 119 +/- 35 mm Hg iNO versus 41 +/- 7 mm Hg control, p < 0.05), and reduced MPO activity by 79% (p < 0.05). We conclude that low dose iNO increases pulmonary blood flow, without worsening pulmonary edema, and decreases lung neutrophil accumulation in severe experimental HMD. We speculate that in addition to its hemodynamic effects, low dose iNO decreases early neutrophil recruitment and may attenuate lung injury in severe HMD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Inhalation
  • Animals
  • Capillary Permeability / drug effects*
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Hemodynamics / drug effects
  • Humans
  • Hyaline Membrane Disease / blood
  • Hyaline Membrane Disease / drug therapy*
  • Hyaline Membrane Disease / etiology
  • Infant, Newborn
  • Leukocyte Count
  • Lung / blood supply*
  • Neutrophils / drug effects*
  • Nitric Oxide / pharmacology*
  • Pulmonary Edema / drug therapy*
  • Pulmonary Gas Exchange / drug effects
  • Respiration, Artificial
  • Sheep


  • Nitric Oxide