Animal Models of Pphn and Vasoconstrictor Signaling in Hypoxia

Neonatal pulmonary hypertension (PH) is a spectrum of disorders caused by in utero and postnatal insults to the developing pulmonary circulation. The clinical presentation can be sudden or insidious. Persistent pulmonary hypertension of the newborn (PPHN) manifests acutely in the immediate perinatal period, often accompanying life-threatening processes, including sepsis and hypoxic-ischemic events. In infants with chronic cardiopulmonary disorders, PH may be clinically unrecognized until the infant is dying from right-sided heart failure. The breadth of knowledge needed to understand the pathophysiology and devise therapies for the broad spectrum of neonatal PH has led to the creation of numerous experimental models in animals at different developmental stages. To create PH, investigators manipulate environmental and hemodynamic conditions known to impact pulmonary vascular tone and/or structure. To achieve meaningful translational relevance to human newborns, the ideal stimulus both elevates tone and causes pertinent structural changes in the pulmonary vasculature, mimicking the pathophysiology of human newborns with treatment-resistant PH.