Does Inhaled Nitric Oxide (No) Modify Lung Function and Oxidative Stress Parameters in Experimental Hyaline Membrane Disease (Hmd)? 231

Background: Interaction between NO and superoxide promotes peroxynitrite production. Thus, mechanisms exist by which inhaled NO may induce oxidant-mediated tissue injury. To test this hypothesis, we studied in experimental HMD the effects of inhaled NO on oxydative stress and lung function parameters. Method: Eighteen moderately premature lambs(130 d gestation, term=147 d) were randomly assigned to treatment with 20 ppm inhaled NO or control. After 5 hours of mechanical ventilation, static lung compliance (C_st) was calculated at 10 ml/kg of tidal volume. Functional residual capacity (FRC), and carbon monoxide diffusing capacity (DLCO) were measured by using the “single breath method”. Then, the lambs were killed. Malondialdehyde level (MDA) and total antioxydant status (TAS) were measured in circulating blood, and MDA, glutathion reductase (GR), glutathion peroxydase (GP), and reduced glutathion (GSH) were measured on lung tissues. Results: C_st and FRC were not significantly different in the NO (n=8) vs. control group (n=10) (C_st: 1.07 ± 0.61 vs 1.03± 0.40 ml.cmH₂O^-1.kg^-1; FRC: 8.73 ± 3.27 vs 10.65 ± 3.74 ml.kg^-1). In spite of similar mechanical properties of the lung in both groups, specific DLCO was increased in the NO group(DLCO:.0106 ±.0070 vs.0052±.0023ml.min¹.mmHg¹.ml^-1: p<0.05). MDA and TAS blood levels, and MDA, GR, GP and GSH on lung tissues did not differ significantly between the 2 groups. Conclusion: no deleterious effects of short term NO inhalation (5 hours) could be demonstrated neither on mechanical lung properties nor on oxydative stress parameters in premature lambs with HMD. Increased lung transfer capacity in the NO group probably results from increased pulmonary blood flow.