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.
