FATE OF THE TYPE-II PNEUMOCYTE FOLLOWING TRACHEAL OCCLUSION IN-UTERO - A TIME-COURSE STUDY IN FETAL SHEEP

Tracheal occlusion in utero has been shown to cause accelerated fetal lung growth and is now being considered as a therapeutic modality for pulmonary hypoplasia. We report the effects of tracheal ligation on th e surfactant-producing type II pneumocyte population. Three groups of fetal lambs underwent tracheal ligation of 2 weeks', 4 weeks' and 6 we eks' duration, respectively, and all were sacrificed at 136 days' gest ation (9 days pre-term). Nonoperated twins served as controls. The typ e II pneumocyte population was studied morphometrically using a combin ation of anti-surfactant protein B immunohistochemistry and computer-a ssisted stereologic morphometry at light and electron microscopic leve ls. Single-factor ANOVA was used for statistical analysis. Two weeks o f tracheal ligation resulted in doubling of the total lung volume as a result of airspace distension and, to lesser extent, growth of the ti ssue compartment. With increasing duration of tracheal ligation, there was no additional lung growth. However, more prolonged tracheal occlu sion was found to result in significant reduction of the surfactant sy stem, as reflected in the marked decrease of total pneumocyte type II volume (3.14 cm(3), 0.95 cm(3), and 0.46 cm(3), after 2, 4, and 6 week s of ligation, compared with 5.96 cm(3) for controls) and total pneumo cyte type II number (13.9 x 10(9), 3.8 x 10(9), and 2.4 x 10(9), compa red with 53.2 x 10(9) for controls). Ultrastructural analysis of the t ype II cells in obstructed lungs showed vacuolar degenerative changes that, after 6 weeks of ligation, were apparently irreversible. In uter o tracheal ligation causes fetal lung hyperplasia, but results in redu ction of and injury to the surfactant-producing cell population. Befor e tracheal occlusion can find widespread clinical application, its pat hophysiology needs to be further elucidated.