ObjectiveTo determine whether inhaled nitric oxide (NO) may alter pulmonary vascular permeability and respiratory function in an in vivo model.DesignProspective, randomized, controlled, experimental study.SettingUniversity experimental pharmacology laboratory.SubjectsMechanically ventilated newborn piglets, 1 to 2 days old, exposed to 100% oxygen for 76 hrs.InterventionsThe piglets were randomly assigned either to a treatment group receiving 20 ppm inhaled NO from the onset of ventilation (n = 5) or to a control group (n = 6) receiving no treatment.Measurements and Main ResultsThe main variables studied were gas exchange (PaO2/FIO2ratio, lung diffusing capacity), respiratory mechanics (static compliance of the respiratory system, stat, quasi-static hysteresis area, functional residual capacity), and pulmonary vascular permeability assessed by simultaneous intravenous administration of iodine-125-labeled albumin and chromium-51-labeled red blood cells. Extravascular albumin space of the lung and dry lung weight were significantly higher in the NO group vs. the control group (albumin space, 1.08 +/- 0.16 vs. 0.70 +/- 0.26 [SD] mL/kg body weight [p < .05]; dry lung weight, 3.20 +/- 0.34 vs. 2.66 +/- 0.14 g/kg body weight [p < .05]). Moreover, the hysteresis area was higher from 24 hrs of NO exposure. Conversely, NO inhalation altered neither the extravascular lung water content (12.98 +/- 2.79 mL/kg body weight in the NO group vs. 12.18 +/- 2.26 mL/kg body weight in the control group [not significant]) nor the main respiratory mechanical variables (static compliance, functional residual capacity) and gas exchange (lung diffusing capacity, PaO2/FIO2ratio).ConclusionThese results do not support the hypothesis that NO inhalation combined with hyperoxia can alter the main lung-function variables in neonates. However, it may induce an increase in lung vascular protein leakage. The pathophysiologic consequences of this finding remain to be elucidated. (Crit Care Med 1999; 27:1168-1174)