Combined Effects of Inhaled Nitric Oxide and Hyperoxia on Pulmonary Vascular Permeability and Lung Mechanics 1751

Potential beneficial and/or detrimental effects of inhaled NO on oxidant-induced lung injury have not been fully investigated in newborn infants. The purpose of this investigation was to examine whether inhaled nitric oxide (NO) may alter pulmonary vascular permeability and respiratory function in mechanically ventilated newborn piglets -1 to 2 days old-, exposed to 100% O₂ for 76 hours. They were randomly assigned to treatment with 20 ppm inhaled NO (n=5) from the onset of ventilation or control (n=6). Peak inspiratory pressure was set to maintain PaCO₂ between 35 and 45 mmHg. The other ventilator parameters were not changed during the course of the study (FiO₂=1; PEEP=5cmH2O; RR=25/min). The main studied parameters were gas exchange (PaO₂/FiO₂ ratio, lung diffusing capacity=DLCO), respiratory mechanics (static compliance of the respiratory system=Crs,stat measured at 5, 10, 15, and 20 ml/kg during inspiration and expiration, quasi-static hysteresis area, functional residual capacity=FRC) and pulmonary vascular permeability assessed by simultaneous intravenous administration of ¹²⁵I-labeled albumin and ⁵¹Cr-labeled red blood cells. PaO₂/FiO₂ decreased significantly between 2 and 76 hours of 100% O₂ exposure in the control and the NO groups (from 388±63 to 225±63 and from 375±84 to 200±64 mmHg respectively). The extravascular albumin space of the lung and the dry lung weight were significantly higher in the NO group versus control group (Alb space: 1.08 ± 0.16 ml / kg body weight versus 0.70 ±0.26 ml / kg body weight and dry lung weight: 3.20 ± 0.34 g / kg body weight versus 2.66 ± 0.14 g / kg body weight respectively). Moreover, hysteresis area was higher from 24 hours of NO exposure. Conversely, NO inhalation did alter neither the extravascular lung water content (12.98 ± 2.79 ml / kg body weight in the NO group versus 12.18 ± 2.26 ml / kg body weight in the control group; NS), nor the main respiratory mechanic parameters (Crs,stat, FRC) and gas exchange (DLCO, PaO₂/FiO₂ ratio). In conclusion, our results do not support the hypothesis that NO inhalation combined with hyperoxia may alter the main lung function parameters in neonates. However, it may induce an increase in lung vascular protein leakage. Pathophysiological consequences of this finding remain to be elucidated.