Pathophysiologic mechanisms of persistent pulmonary hypertension of the newborn

Persistent pulmonary hypertension of the newborn (PPHN), among the most rapidly progressive and potentially fatal of vasculopathies, is a disorder of vascular transition from fetal to neonatal circulation, manifesting as hypoxemic respiratory failure. PPHN represents a common pathway of vascular injury activated by numerous perinatal stresses: hypoxia, hypoglycemia, cold stress, sepsis, and direct lung injury. As with other multifactorial diseases, a single inciting event may be augmented by multiple concurrent/subsequent phenomena that result in differing courses of disease progression. I review the various mechanisms of vascular injury involved in neonatal pulmonary hypertension: endothelial dysfunction, inflammation, hypoxia, and mechanical strain, in the context of downstream effects on pulmonary vascular endothelial‐myocyte interactions and myocyte phenotypic plasticity. © 2005 Wiley‐Liss, Inc.