Bronchopulmonary dysplasia and early prophylactic inhaled nitric oxide in preterm infants: Current concepts and future research strategies in animal models

We reviewed the literature on the use of inhaled nitric oxide and the influence of supplemental oxygen on bronchopulmonary dysplasia (BPD), and the role of endogenous nitric oxide-synthase, vascular endothelial growth factor, the interplay of nitric oxide and superoxide, protein nitration and the nuclear factor kappa B-pathway. BPD is a major cause of neonatal mortality and morbidity leading to arrested lung development in newborns. Several studies indicate that inhaled nitric oxide (iNO) improves pulmonary angiogenesis, lung alveolarization, distal lung growth and pulmonary function in preterm infants. Given the inconclusive results of clinical studies, however, it is unclear which subpopulations of infants might benefit. Moreover, data on iNO are conflicting whether exogenous nitric oxide is protective or damaging in the presence of hyperoxia. The toxicology of iNO is poorly understood and its potential interaction with oxygen has to be considered given that infants treated with iNO are also supplemented with oxygen. The underlying mechanisms of the effects of iNO in the newborn lung need further analysis. New data clarifying the role of endogenous nitric oxide-synthases, vascular endothelial growth factor (VEGF), the interplay of nitric oxide and superoxide, and protein nitration with concurrent iNO-therapy might answer some of these questions.