Pathogenesis and Physiologic Mechanisms of Neonatal Pulmonary Hypertension: Preclinical Studies

Neonatal pulmonary hypertension (PH) is a devastating disorder of the pulmonary vasculature characterized by elevated pulmonary vascular resistance and mean pulmonary arterial pressure. Occurring predominantly because of maldevelopment or maladaptation of the pulmonary vasculature, PH in neonates is associated with suboptimal short-term and long-term outcomes because its pathobiology is unclear in most circumstances, and it responds poorly to conventional pulmonary vasodilators. Understanding the pathogenesis and pathophysiology of neonatal PH can lead to novel strategies and precise therapies. The review is designed to achieve this goal by summarizing pulmonary vascular development and the pathogenesis and pathophysiology of PH associated with maladaptation, bronchopulmonary dysplasia, and congenital diaphragmatic hernia based on evidence predominantly from preclinical studies. We also discuss the pros and cons of and provide future directions for preclinical studies in neonatal PH.