PHYSIOLOGY OF THE PERINATAL PULMONARY CIRCULATION
Pulmonary vascular resistance (PVR) is high throughout fetal life, especially compared with the low resistance of the systemic circulation. As a result, the fetal lung receives less than 3% to 8% of combined ventricular output, with most of the right ventricular output crossing the ductus arteriosus to the aorta. In addition to structural maturation and growth of the developing lung circulation, the vessel wall also undergoes functional maturation, leading to enhanced vasoreactivity during fetal life. Mechanisms that contribute to high basal PVR in fetuses include low oxygen tension, relatively low basal production of vasodilator products (e.g., prostacyclin [PgI2] and nitrous oxide [NO]), increased production of vasoconstrictors (including endothelin-1), and altered smooth muscle cell reactivity (e.g., enhanced myogenic tone). During development, the fetal pulmonary circulation is characterized by a progressive increase in responsiveness to vasoactive stimuli, including changes in oxygen tension.
Postnatal survival depends on the successful transition of the fetal pulmonary circulation from its high resistance state in utero to a low-resistance, high-ﬂow vascular bed within minutes after delivery. This decrease in PVR allows for the eightfold increase in pulmonary blood ﬂow that is necessary for the lungs to serve their postnatal function for gas exchange (see Plate 1-43). Mechanisms that contribute to the normal decrease in PVR at birth include vasodilation caused by birth-related stimuli, such as increased oxygen tension, ventilation, and shear stress, and altered production of several vasoactive products, especially the enhanced release of NO and prostacyclin. In addition, high pulmonary blood ﬂow abruptly causes a structural reorganization of the vascular wall that includes ﬂattening of the endothelium and thinning of smooth muscle cells and matrix. Thus, the ability to accommodate this marked increase in blood ﬂow requires rapid functional and structural adaptations to ensure the normal postnatal decrease in PVR.
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 a major clinical problem, contributing signiﬁcantly to high morbidity and mortality in both full-term and premature neonates.