Pulmonary Development in the Fetal Lamb with Severe Bladder Outlet Obstruction and Oligohydramnios: A Morphometric Study

Abstract

The lethal feature of male newborns with severe bladder outlet obstruction and oligohydramnios is pulmonary hypoplasia. We report a fetal lamb model of bladder outlet obstruction created in the early second trimester, and morphometric analysis of the profound pulmonary hypoplasia that resulted. At 55 to 65 days of gestation 8 consecutive male fetuses underwent surgical clipping of the urethra and urachus near the abdominal wall. A sham operation was performed in 1 female fetus. The lambs were delivered by cesarean section 10 weeks later. The right lungs were immediately fixed at a distending pressure of 25 cm. water. The results of the morphometric studies were compared to control animals from our earlier study of normal fetal lamb lung development; slides for both studies were scored in a blind, randomized fashion by 1 of us (S. G. D.). Although mean body weights for the groups were similar, mean right lung volume in the operated lambs was 63.8 cM.3 compared to 158 cM.3 in the control animals and 137 cM.3 in the sham operated fetus (p less than 0.0005). Relative volume of respiratory tissue was 87 per cent in the operated animals, and 92 per cent in the controls and the sham operated fetus (p less than 0.0005). Microscopic morphometry revealed an increased relative volume of inter-alveolar tissue in the experimental animals (35 compared to 23 per cent in the normal lambs, p less than 0.05), with a corresponding decrease in relative airspace volume. Alveolar numerical density and alveolar surface density were not statistically different between the groups, although total alveolar number and surface area were substantially decreased in the operated lambs due to the reduced mean lung volume. Mean alveolar wall thickness was increased at 3.6 microM. in the operated group versus 2.1 microM. in the normal group (p less than 0.0005) and 2.8 microM. in the sham operated fetus. Thus, the lung in the lamb with severe bladder outlet obstruction is hypoplastic and immature.