Invited Review: Clearance of lung liquid during the perinatal period

Abstract

Barker, Pierre M., and Richard E. Olver. Invited Review: Clearance of lung liquid during the perinatal period. J Appl Physiol 93: 1542-1548, 2002; 10.1152/japplphysiol.00092.2002.-At birth, the distal lung epithelium undergoes a profound phenotypic switch from secretion to absorption in the course of adaptation to air breathing. In this review, we describe the developmental regulation of key membrane transport proteins and the way in which epinephrine, oxygen, glucocorticoids, and thyroid hormones interact to bring about this crucial change in function. Evidence from molecular, transgenic, cell culture, and whole lung studies is presented, and the clinical consequences of the failure of the physiological mechanisms that underlie perinatal lung liquid absorption are discussed. lung liquid; sodium absorption; chloride secretion; epithelial sodium channel; cystic fibrosis transmembrane conductance regulator THE MECHANISMS RESPONSIBLE for lung liquid clearance during the neonatal period develop gradually during the latter part of the third trimester of pregnancy, but the phenotypic switch of the lung epithelium from net secretion to net absorption, triggered by events at birth, is sudden. Although lung liquid absorption at birth is "a performance without rehearsal," the lung may be called on for an encore in later life when these same mechanisms are activated to clear accumulated edema liquid.Many of the early studies of perinatal lung liquid clearance, which were mostly undertaken on the intact lungs of rabbits and sheep in the 1970s and 1980s, provided information in vivo on the time course and regulation of lung liquid clearance in a fully integrated physiological context. These data have been supported and augmented in the past decade by cloning of genes that regulate transepithelial ion transport [particularly the sodium pump (Na ϩ -K ϩ -ATPase) and the epithelial Na ϩ channel (ENaC)] and the use of molecular approaches that have uncovered information at a subcellular level.

Effects of labor contractions on catecholamine release and breathing frequency in newborn rats.

“…As compared with babies exposed to a trial of labor, babies delivered by elective cesarean section (even near term) show (a) an increased risk of respiratory morbidity (Cohen & Carson, 1985;Zanardo et al, 2004); (b) a fivefold increase in the likelihood of persistent pulmonary hypertension (Levine, Ghai, Barton, & Strom, 2001); (c) lower dynamic lung compliance (Faxelius, Hagnevik, Lagercrantz, Lundell, & Irestedt, 1983) and higher functional residual capacity, possibly as an adaptation to elevated lung water content (Hagnevik, Lagercrantz, & Sjoqvist, 1991); (d) increased incidence of postpartum respiratory distress (Irestedt, Lagercrantz, & Belfrage, 1984); (e) decreased protection from oxidative stress (Buhimschi, Buhimschi, Pupkin, & Weiner, 2003); and (f) delayed neurodevelopmental status (Otamiri, Berg, Ledin, Leijon, & Lagercrantz, 1991;Otamiri, Berg, Ledin, Leijon, & Nilsson, 1990). Animal studies of labor's effects on the fetus and newborn, conducted almost exclusively in the precocial sheep fetus, have revealed important roles of birth-related catecholamines, including stimulating lung liquid absorption (reviewed by Barker & Olver, 2002), sustaining metabolic and cardiac homeostasis (Padbury et al, 1987), and providing protection from hypoxia (C. T. Jones, 1980). Labor-induced catecholamine release may provide an important mechanism underlying the neonate's process of adapting to extrauterine conditions and the recruitment of vital postnatal behaviors (Ronca, Abel, & Alberts, 1996).…”

Lentiviral transduction of the murine lung provides efficient pseudotype and developmental stage-dependent cell-specific transgene expression

“…In utero, the lung is primarily a secretory organ although amniotic fluid is drawn into the lung by simulated breathing movements prior to birth. 38 These breathing movements are of sufficient intensity and frequency at 16 days pcm to allow transduction of the fetal mouse airway after intra-amniotic injection. 3 Immediately postpartum, the lung epithelium switches to fluid hyperabsorption in order to clear the lung of fluid and facilitate gaseous exchange.…”

Primary pulmonary lymphangiectasia in infancy and childhood

“…The reason these infants do not present at birth is difficult to explain. At birth, additional stress is placed on interstitial clearance mechanisms as the large volume of foetal lung liquid that occupies the alveolar compartment during gestation is absorbed from the lung lumen to make way for air-breathing [23]. Whilst some alveolar fluid is cleared via the lung lymphatics, resulting in an increase in lung lymph flow at birth, most of lung liquid reabsorbed from the alveolar space is thought to pass directly into the foetal circulation [24].…”