Lung growth induced by tracheal occlusion in the sheep is augmented by airway pressurization

Abstract

Background/Purpose: Prenatal tracheal occlusion (TO) has been shown to accelerate lung growth, yet the mechanism for this effect is poorly understood. Increased intratracheal pressure (ITP) with accumulation of lung fluid and secondary airway distension (stretch) may provide a mechanical stimulus for growth. In this study, ITP after TO is measured continuously, and the effect of altering ITP on lung growth is examined.Methods: Fetal lambs of 115 to 120 days of gestation (term, 145 days) underwent placement of an intratracheal catheter and an amniotic fluid reference catheter. First, ITP was monitored continuously in normal controls (n = 4) and in fetuses undergoing TO (n = 6). In a subsequent study, 2 groups of fetuses were compared. In the TO group (n = 5) ITP was monitored after TO. In the pressurized group (n = 5) ITP was maintained at 7 to 8 mm Hg by a continuous servo regulated pump that maintains a preset pressure by lactated Ringers infusion. The animals were killed after 4 days, and lung growth was compared.Results: In the control animals, ITP remained constant at 0.4 to 1.5 mm Hg. In the TO animals, ITP increased gradually during the initial 24 hours and plateaued at 4 to 5 mm Hg. In the second set of animals, ITP in the pressurized group was maintained at approximately 8 mm Hg using the infusion system. Lung volume (135.7 ± 17.4 v 95.2 ± 14.8 mL/kg P < .01), lung weight to body weight (6.70 ± 0.73 v 5.33 ± 0.77%; P < .05), whole right lung dry weight (3.10 ± 0.22 v 2.63 ± 0.20 mg/kg; P < .05), and right lung DNA and protein contents (87.3 ± 6.0 v 74.6 ± 8.1 mg/kg, 2,310 ± 248 v 1,860 ± 196 mg/kg, respectively; P < .05) were increased significantly in the pressurized group compared with the TO group. Morphometry confirmed greater volume of respiratory region and increased alveolar surface area in the pressurized lung.Conclusions: TO results in a gradual increase in ITP over 15 to 24 hours, which plateaus at 4 to 5 mm Hg. Further increasing ITP by infusion of crystalloid significantly augments lung growth beyond that observed with TO alone. These data support the hypothesis that airway pressure and secondary mechanical stretch are the primary stimuli of TO induced lung growth.