Abnormal Vasoreactivity in the Pathophysiology of Persistent Pulmonary Hypertension of the Newborn

Abstract

1. Steven H. Abman, MD1,* 1. 2. *Professor, Department of Pediatrics, University of Colorado School of Medicine and The Children’s Hospital, Denver CO. After completing this article, readers should be able to: 1. Describe the factors that modulate the transition of pulmonary circulation from in utero to after birth. 2. Delineate temporal changes in pulmonary vascular resistance during fetal life. 3. List the substances that play a role in vasoregulation of normal fetal pulmonary circulation. 4. Delineate the role of nitric oxide in increasing pulmonary blood flow at birth. 5. Describe the common physiologic characteristics of persistent pulmonary hypertension of the newborn. 6. Delineate how abnormalities in production and responsiveness to nitric oxide affect developing lung circulation. 7. Explain why inhaled nitric oxide therapy may not be effective in all cases of pulmonary hypertension. Successful adaptation of the newborn to postnatal conditions requires a dramatic transition of the pulmonary circulation from a high resistance state in utero to a low-resistance state within minutes after birth. This fall in pulmonary vascular resistance (PVR) allows for a nearly 10-fold rise in pulmonary blood flow that ensures that the lung can assume its postnatal role in gas exchange. Over the past 50 years, experimental studies have demonstrated that several mechanisms contribute to the normal fall in PVR at birth, including the establishment of a gas-liquid interface in the lung, increased oxygen tension, rhythmic distension of the lung (respiration), and shear stress. In addition to these physical stimuli, pulmonary vascular tone is modulated by altered production of vasoactive products, especially the release of potent vasodilator substances, such as nitric oxide (NO) and prostacyclin (PgI2). Within minutes of this vasodilator response, increased pulmonary blood flow 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. Thus, the ability to accommodate this marked rise in blood flow requires rapid functional and structural adaptations to ensure that the normal postnatal fall in …