ABSTRACT
During the course of birth, a fascinating array of biologic processes act in unison to support the normal transition of the human fetus to become an air-breathing newborn. The centerpiece of this remarkable progression is the dramatic transformation of the fetal pulmonary circulation. In a very short period of time at birth, the fetal pulmonary arteries rapidly dilate in response to birth-related stimuli including a marked rise in oxygen tension, which contributes to the eightfold increase in pulmonary blood flow, allowing for the lung to successfully function in its essential role for postnatal gas exchange. Failure to achieve this drop in pulmonary vascular resistance at birth leads to profound hypoxemia due to intrapulmonary right to left shunt, with high morbidity and mortality. Hypoxemia, a common feature that accompanies diverse antenatal stresses in the developing fetus significantly disrupts this course. Due to a variety of cellular, intracellular, and molecular mechanisms that are induced by hypoxia, the pulmonary arterial system remains highly contracted at birth but also undergoes pathologic remodeling that includes impaired growth and structural changes in the vascular wall of arteries throughout the distal lung. These abnormal structural features contribute to the pathobiology of persistent pulmonary hypertension of the newborn (PPHN), a clinical syndrome that is characterized by pulmonary hypertension, high pulmonary vascular resistance and significant systemic hypoxemia. This chapter briefly reviews the contribution of aberrant vascular structure to sustained hypoxemia in severe PPHN.
