Lung Hypoplasia Can Be Reversed by Short-Term Obstruction of the Trachea in Fetal Sheep

Abstract

i\HSTR,A T Vol. 38, No.5, 1995 Primed ill U.S.A.Our aim was 10 determine whether an existing lung growth deficit could be reversed, in utero, by short-term (6 d) obstruction of the fetal trachea. Chronically catheterized fetal sheep (term -145 d) were divided into four groups: 1) no treatment (control); 2) continuous lung liquid drainage to induce lung hypoplasia Th roughout mos t of gestation the lungs are filled with a liquid that is secreted across the pulmonary epithelium and leaves the lungs via the trachea. It is well established that the vo lume of liqu id retained wit hin the future airways is critical for normal lung growth and deve lopment. Obstruct ion of the feta l trach ea, wh ich causes secreted lung liquid to accumulate in the future airways resulting in increased expansion of the lungs (1) , greatly increases lung growth (2, 3). Conversely, prolonged drainage of feta l lung liqu id to the exterior causes lung deflation and a near cessation of lung grow th (2, 3). We have recently show n that the increase in lung growth induced by tracheal obstruction is ver y rapi d and occurs within 7 d of blocking the feta l trachea (4). Such results have led to the suggestion that short-term per iods of tracheal obstruct ion ma y rapi dly reverse an existing lung growth deficit in utero (4, 5).Inadequ ate lung growth during feta l life res ults in pul monary hypoplasi a at birth and is a common cause of perinatal mor- mg/kg versus 94 :t 7 mg/kg). Reestablishing tracheal flow for 6 d (drain and reconnect) increased fetal lung wet weights (19.2 :t 1.6 g/kg), but not total DNA contents (106 :t 9 mg/kg), compared with lung liquid drained fetuses (drain). After 6 d of tracheal obstruction (drain and obstruct) lung liquid volumes, wet lung weights, and total protein contents (weight, 28.6 :t 2.8 g/kg; protein, 1376 :t 97 mg/kg) were similar to control values (weight, 34.3 :t 2.6 g/kg; protein, 1506 :t 123 mg/kg); lung DNA contents were less than control but greater than values from lung liquid drained fetuses (drain and obstruct, 140 :t 9 mg/kg versus drain, 94 :t 7 mg/kg). We conclude that obstruction of the trachea can reverse an existing fetal lung growth deficit in approximately 6 d, whereas merely restoring tracheal continuity does not increase fetal lung growth. (Pediatr Res 38: 690-69 6, 1995) bidity and mortality in new born infants (6, 7). To avoid the postnatal consequences of fetal lung hypoplasia in humans, atte mpts have been made to surgically treat this condition in utero, before the lungs are required for gas exchange. However, these treatments have principally foc used on correcting the und erlying abnormality rather than attempting to acce lerate lung growth directly (8, 9). As increased fe tal lung expansion, resulting from tracheal obstruction, is a potent and rapid way of accelerating fetal lung gro wth (2-4), we considered it possible tha t trac hea l obstruction may rapi dly reve rse an exi sting lung growth defici t in utero. The aim of this study was to determine whether fe tal lun...

The long-term follow-up of patients with a congenital diaphragmatic hernia: a broad spectrum of morbidity

“…Occlusion of the fetal trachea was shown to stimulate fetal growth in a variety of animal models [34][35][36][37][38][39][40]. On the other hand, prematurity caused by the intervention itself can be detrimental.…”

Analysis of the conducting airway system in the lung: A new method combining morphometry with mathematical modeling for airway classification

“…The sheep lung has been used widely in scientific research to study aspects of normal development (Alcorn et al, 1981;Davey et al, 1998;Davies et al, 1988) as well as pathological processes (Hashim et al, 1995;Hedrick, et al, 1997;Lipsett et al, 1998;Lipsett, et al, 1997;Nardo et al, 1995;Pringle, 1984;Rees et al, 1991). It is considered to be a valuable subject of study because it shows similarities to the human lung (Liggins and Kitterman, 1981;O'Rahilly and Boyden, 1973;Pringle, 1986).…”

Visualisation and Measurement of Tracheal Diameter in the Sheep Fetus: An Ultrasound Study with Stereomicroscopic Correlation

“…Occlusion of the fetal trachea causes liquid to accumulate within the future airways and this is a potent stimulus for lung growth [11]. This procedure, the so-called PLUG technique, has been proposed as a potential method for stimulating lung development in fetuses with pulmonary hypoplasia [12,13]. Another research field using the ovine model focuses on the early treatment of inherited diseases by topical application of gene therapy vectors to selected organ systems at mid to late gestation [14] .…”