Fetal lung growth. Influence of pulmonary arterial flow and surgery in sheep.
Aberrant pulmonary arterial flow has been associated with pulmonary hypoplasia, which is a common cause of death in newborns. The current experiments were designed to confirm whether interruption of postductal main pulmonary artery (MPA) flow causes pulmonary hypoplasia. In addition, the effect of fetal surgery on lung growth was investigated. Fetal sheep, instrumented at 107 to 115 d gestation (MPA ligated [n = 5], sham operated [n = 3], and monitored [no thoracotomy, n = 5]), and unoperated twin fetuses (140-d controls, n = 5) were used for analysis of lung growth at 136 to 140 d gestation. Morphometric measurement of lung tissue volumes and assays of DNA, protein, and saturated phosphatidylcholine (SPC) were used to assess lung growth. MPA ligation significantly decreased lung growth and maturation as indicated by decreased surface area and volumes of fine nonparenchyma, future airspace, and parenchymal tissue, and by decreased lung weights, total DNA, protein, and SPC content. There was a significant increase in the volume percentage of coarse nonparenchyma and a decrease in the volume percentage of future airspace. The pattern of lung growth after MPA ligation suggests that growth of peripheral airspace and parenchymal tissue components does not occur, resulting in a significant decrease in the amount of new tissue formed and delayed tissue maturation. Fetal surgery significantly changed only DNA, protein, and SPC content. Studies of the regulation of lung growth must consider the role of pulmonary arterial flow and the smaller, but significant effects of fetal surgery.