Reversible tracheal obstruction in the fetal sheep: Effects on tracheal fluid pressure and lung growth

Abstract

Congenital diaphragmatic hernia (CDH) continues to carry high morbidity and mortality. A number of treatment modalities including extracorporeal membrane oxygenation and in utero repair have improved the mortality rate only minimally. With this condition, there is often insufficient lung mass at birth and persistent pulmonary hypertension postnatally. Experimental fetal tracheal ligation has been shown to increase lung growth in utero and to reduce the hernial contents in CDH. The purpose of this study was to determine the effect of reversible fetal tracheal occlusion on tracheal pressure and lung development. Nine fetal sheep were divided into two groups. Group 1 had intratracheal balloons placed, and the balloons were left inflated for 21 to 28 days. Group 2 consisted of littermates that served as controls. They either had uninflated balloons placed or were left unoperated. Tracheal pressure measurements were recorded periodically, and the amniotic fluid pressure served as a reference. The animals were killed near term, and the lungs, heart, and liver were weighed and corrected for body weight. Standard morphometry was used to compare the lungs further, and the lung DNA and protein content were measured. Tracheal damage from the balloon catheter also was assessed. The tracheal pressure was 3.85 (±.49 SE) mm Hg in experimental animals, and it averaged −0.27 (±.27 SE) mm Hg in controls ( P < .0001). Tracheal occlusion increased lung weight and volume by two to three times ( P < .0001 and P < .0006, respectively) while heart and liver weights remained similar to those of controls. The airspace fraction and radial alveolar counts were increased ( P = .044 and P = .0002, respectively), and the alveolar number per body weight was doubled ( P < .0001). However, the alveolar number per lung volume was preserved, as were the DNA and protein content per unit weight of lung tissue. The chronic indwelling balloon catheter caused some mucosal and submucosal damage at the balloon site and proximal to it. These results show that tracheal occlusion leads to an elevation of intratracheal pressure that is associated with a tremendous increase in lung growth over a short period in third-trimester fetal sheep. The techniques used in this experiment can be easily modified for use with endoscopic surgical equipment.