ABSTRACT
Persistent pulmonary hypertension of the newborn (PPHN) occurs when the pulmonary circulation fails to adapt to postnatal life. PPHN complicates the course of approximately 10% of term and preterm infants with respiratory failure and increases the risk of pulmonary morbidity and death. Pulmonary hypertension (PH) also increases morbidity and mortality in extremely preterm infants with bronchopulmonary dysplasia (BPD), a common chronic lung disease of prematurity. Malnutrition in very preterm infants is another risk factor for PH and BPD. In vivo and in vitro studies using a fetal lamb model of PPHN have revealed a central role for reactive oxygen species (ROS), which can disrupt the normal fetal to newborn transition as well as inducing pulmonary vascular remodeling. Newborn rodents exposed to chronic hyperoxia develop PH, pulmonary vascular remodeling, and alveolar simplification characteristic of preterm infants with BPD. Studies using this model indicate a role for ROS in PH and in abnormal pulmonary vascular and parenchymal development. Postnatal malnutrition and chronic hypoxia both induce PH in newborn rats by mechanisms involving increased ROS. This chapter discusses the sources of elevated ROS in the above models and identifies downstream targets of ROS that trigger pulmonary hypertension including impaired hypoxia inducible factor signaling.
