Combined effects of inhaled nitric oxide and hyperoxia on pulmonary vascular permeability and lung mechanics

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Abstract
To determine whether inhaled nitric oxide (NO) may alter pulmonary vascular permeability and respiratory function in an in vivo model. Prospective, randomized, controlled, experimental study. University experimental pharmacology laboratory. Mechanically ventilated newborn piglets, 1 to 2 days old, exposed to 100% oxygen for 76 hrs. The 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. The main variables studied were gas exchange (PaO2/FIO 2 ratio, 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/FIO 2 ratio). These 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)