ABSTRACT
Insights into the physiology and treatment of persistent pulmonary hypertension of the newborn (PPHN) begin with an understanding of normal development of the lung circulation and its changes immediately after birth (p. 62). Successful adaptation of the newborn to postnatal conditions requires a dramatic transition of the pulmonary circulation, from its high resistance state in utero to its low resistance state within minutes after birth. This fall in pulmonary vascular resistance (PVR) allows for the roughly eightfold rise in pulmonary blood flow at birth, thereby enabling the lung to assume its postnatal role in gas exchange. Several mechanisms contribute to the normal fall in PVR at birth. These include the establishment of a gas-liquid interface in the lung, increased oxygen tension, rhythmic distention of the lung (ventilation), and shear stress.25,26,59,130,131 Birthrelated stimuli cause vasodilation through changes in the production of vasoactive products, including increased release of potent vasodilators, including nitric oxide (NO) and prostacyclin (PgI2), and decreased activity of endogenous vasoconstrictors, such as endothelin-1 (ET-1).5,25,32,33,88,89,156 Within minutes of this vasodilator response, high pulmonary blood flow abruptly increases shear stress and distends the vasculature, causing a ‘structural reorganization’ of the vascular wall that includes flattening of the endothelium and thinning of smooth muscle cells and matrix.12,58 Thus, the ability to accommodate this marked rise in blood flow requires rapid functional and structural adaptations to ensure the normal postnatal fall in PVR. Following this early period of
over the next days to weeks of life due to vascular remodeling and growth in the normal infant.59,130,131
Some infants fail to achieve or sustain the normal decrease in PVR at birth, leading to severe respiratory distress and hypoxemia, which is referred to as persistent pulmonary hypertension of the newborn (PPHN). PPHN is not a single disease, but rather, it is a clinical syndrome that occurs in association with diverse neonatal cardiorespiratory disorders, such as meconium aspiration, sepsis, pneumonia, acute respiratory distress syndrome, asphyxia, congenital diaphragmatic hernia, lung hypoplasia, and others.47,73,90,103,142,159 Although striking differences exist between these conditions, these disorders share common pathophysiological features, including high PVR leading to extrapulmonary right-to-left shunting of blood flow across the ductus arteriosus or foramen ovale. PPHN remains a major clinical problem, contributing significantly to high morbidity and mortality in both full-term and premature neonates.106
