3-nitrotyrosine and Respiratory-Distress-Syndrome--Newborn

Inhaled nitric oxide treatment for ventilated premature infants improves survival without bronchopulmonary dysplasia. However, there has been no information regarding possible effects of this therapy on oxidative stress. We hypothesized that inhaled nitric oxide therapy would not influence concentrations of plasma biomarkers of oxidative stress.. As part of the Nitric Oxide Chronic Lung Disease Trial, we collected blood samples at specified intervals from a subpopulation of 100 infants of <1250 g birth weight who received inhaled nitric oxide (20 ppm, weaned to 2 ppm) or placebo gas for 24 days. Plasma was assayed for total protein and for 3-nitrotyrosine and carbonylation by using immunoassays.. The demographic characteristics and primary outcome for the infants were representative of the entire group of infants who were in the Nitric Oxide Chronic Lung Disease Trial. For all infants at baseline, before receiving study gas, the concentration of total protein was inversely correlated with the respiratory severity score, and plasma carbonyl was positively correlated with severity score, supporting an association between oxidative stress and severity of lung disease. Infants who survived without bronchopulmonary dysplasia had 30% lower protein carbonylation concentrations at study entry than those who had an adverse outcome. At each of 3 time points (1-10 days) during exposure to study gas, there were no significant differences between control and treated infants for concentrations of plasma protein, 3-nitrotyrosine, and carbonylation.. Inhaled nitric oxide treatment for premature infants who are at risk for bronchopulmonary dysplasia does not alter plasma biomarkers of oxidative stress, which supports the safety of this therapy.

Topics: Administration, Inhalation; Biomarkers; Bronchopulmonary Dysplasia; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; Female; Humans; Infant, Extremely Low Birth Weight; Infant, Newborn; Logistic Models; Male; Nitric Oxide; Oxidation-Reduction; Oxidative Stress; Predictive Value of Tests; Probability; Prognosis; Proteins; Respiratory Distress Syndrome, Newborn; Risk Factors; Sensitivity and Specificity; Severity of Illness Index; Survival Analysis; Treatment Outcome; Tyrosine

Inhaled nitric oxide (iNO) is an effective adjunct in the treatment of infants with respiratory failure. Although there are clear benefits to this therapy, potential toxicity could result from reactive nitrosylated species.. To evaluate whether iNO therapy is associated with increased serum markers of oxidative stress.. Multiple markers were prospectively evaluated in the serum of term infants with severe respiratory failure treated with iNO for 1 to 72 hours. These were compared to those of patients exposed to greater than 80% oxygen for more than 6 hours and room air controls.. After 24 hours of exposure, the iNO-treated infants had increased serum lipid hydroperoxides (LPO), protein carbonyls and nitrotyrosine residues as well as increased serum total glutathione (GSH) content. The increase in LPO peaked at 24 hours and correlated with the cumulative dose of iNO whereas other markers did not. The presence of chronic lung disease (CLD) did not correlate with serum markers of oxidative injury.. In term infants with respiratory failure, prolonged iNO exposure is associated with a transient increase in markers of oxidative stress, but this finding does not appear to predict the development of CLD.

Topics: Administration, Inhalation; Biomarkers; Bronchodilator Agents; Chronic Disease; Female; Glutathione; Humans; Infant, Newborn; Lipid Peroxides; Male; Nitric Oxide; Oxidative Stress; Prospective Studies; Respiratory Distress Syndrome, Newborn; Tyrosine

We prospectively analyzed airway specimens from 24 newborn infants. Inhaled nitric oxide (< or = 20 ppm for 1 to 4 days to 12 infants) did not affect the concentrations of the lipid peroxidation product, the surface activity, or the cytokines (interleukin-1, granulocyte-macrophage colony-stimulating factor, interleukin-1 receptor antagonist). Nitrotyrosine was detected after 10 days of life in the two infants requiring prolonged ventilation, suggesting toxicity of endogenous nitric oxide.

Topics: Cytokines; Female; Humans; Infant, Newborn; Lipid Peroxidation; Male; Nitric Oxide; Persistent Fetal Circulation Syndrome; Prospective Studies; Respiration, Artificial; Respiratory Distress Syndrome, Newborn; Tyrosine

Activated alveolar macrophages and epithelial type II cells release both nitric oxide and superoxide which react at near diffusion-limited rate (6.7 x 10(9) M-1s-1) to form peroxynitrite, a potent oxidant capable of damaging the alveolar epithelium and pulmonary surfactant. Peroxynitrite, but not nitric oxide or superoxide, readily nitrates phenolic rings including tyrosine. We quantified the presence of nitrotyrosine in the lungs of patients with the adult respiratory distress syndrome (ARDS) and in the lungs of rats exposed to hyperoxia (100% O2 for 60 h) using quantitative immunofluorescence. Fresh frozen or paraffin-embedded lung sections were incubated with a polyclonal antibody to nitrotyrosine, followed by goat anti-rabbit IgG coupled to rhodamine. Sections from patients with ARDS (n = 5), or from rats exposed to hyperoxia (n = 4), exhibited a twofold increase of specific binding over controls. This binding was blocked by the addition of an excess amount of nitrotyrosine and was absent when the nitrotyrosine antibody was replaced with nonimmune IgG. In additional experiments we demonstrated nitrotyrosine formation in rat lung sections incubated in vitro with peroxynitrite, but not nitric oxide or reactive oxygen species. These data suggest that toxic levels of peroxynitrite may be formed in the lungs of patients with acute lung injury.

Topics: Adolescent; Animals; Child; Child, Preschool; Female; Fluorescent Antibody Technique; Humans; Infant; Infant, Newborn; Lung; Male; Microtomy; Nitrates; Rats; Rats, Sprague-Dawley; Respiratory Distress Syndrome, Newborn; Tyrosine