Introduction: In several clinical trials in term infants with respiratory failure, inhaled nitric oxide (INO) has been shown to acutely increase oxygenation and significantly decrease mortality and/or need for ECMO. The long term effects of INO remain largely unknown. Both NO and its metabolites react to form cytotoxic species which may be involved in the development of chronic lung disease. The purpose of this investigation was to determine whether there is increased oxidant stress in the serum of infants receiving INO when compared to normal controls and infants exposed to hyperoxia.

Methods: Serum samples were obtained from three groups of infants; term infants in room air, infants with severe respiratory or cardiac failure requiring > 80% oxygen for > 8 hours and infants with severe respiratory or cardiac failure requiring > 80% oxygen and INO therapy. Those receiving oxygen and INO had 3 samples drawn at approximately 1, 24 and 48 hours after initiation of INO therapy. Samples were assayed for lipid hydroperoxides (LPO), serum glutathione (GSH), total antioxidant status (TAS), protein carbonyls (PC) and serum nitrotyrosine residues (NT).

Results: For the three groups of infants; room air (n=31), oxygen(n=34) and oxygen + INO (n=20), mean birthweight, gestational age and chronological age were similar. Measurement of oxidative markers revealed serum LPO was increased 5 fold in infants treated with INO for 24 hours compared to oxygen treated infants. Serum GSH was increased at 24 hours, but decreased at 48 hours of INO therapy. Immunoreactive PC and NT were visibly increased in INO treated infants compared to oxygen treated infants and the level correlated with the length of INO exposure.

Conclusions: We conclude that INO exposure is associated with evidence of increased oxidant injury as well as decreased antioxidant defenses. Although INO appears to be an important therapy for severe respiratory and cardiac failure, its use may be associated with adverse consequences resulting from oxygen radical injury such as chronic lung disease.