PLASMA 3-NITROTYROSINE IS ELEVATED IN PREMATURE-INFANTS WHO DEVELOP BRONCHOPULMONARY DYSPLASIA

Objective. Premature infants are susceptible to bronchopulmonary dyspl asia (BPD), a chronic lung disease of infancy that appears to be cause d in part by oxidative stress from hyperoxia. To investigate the possi ble role of nitric oxide-derived oxidants such as peroxynitrite in the etiology of BPD, we measured levels of plasma 3-nitrotyrosine, which is produced by the reaction of peroxynitrite with proteins. Patients a nd Methods. Ten premature infants who developed BPD, defined as requir ing supplemental oxygen beyond 36 weeks' postmenstrual age, were ident ified retrospectively from a group of subjects enrolled in a clinical trial of antenatal therapy. Serial plasma samples had been collected o n these infants during the first month of life as part of the trial. S ixteen comparison premature infants were identified from the same popu lation: 5 had no lung disease, 6 had respiratory distress syndrome tha t resolved, and 5 had residual lung disease at 28 days of life that re solved by 36 weeks' postmenstrual age. Plasma 3-nitrotyrosine levels w ere measured using a solid phase immunoradiochemical method. Results. All 3-nitrotyrosine values in infants without BPD were <0.25 ng/mg pro tein, and levels did not change with postnatal age. Plasma 3-nitrotyro sine concentrations were significantly higher in infants with BPD, inc reasing approximately fourfold during the first month of life. For the 20 infants who had blood samples available at 28 days of life, plasma 3-nitrotyrosine levels correlated with the fraction of inspired oxyge n that the infant was receiving (r = 0.7). Conclusion. Plasma 3-nitrot yrosine content is increased during the first month of life in infants who develop BPD. This suggests that peroxynitrite-mediated oxidant st ress may contribute to the development of this disease in premature in fants and that 3-nitrotyrosine may be useful as an ear;ly plasma indic ator of infants at risk for developing BPD.