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Fate of the type II pneumocyte following tracheal occlusion in utero: a time-course study in fetal sheep

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 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 the surfactant-producing type II pneumocyte population. Three groups of fetal lambs underwent tracheal ligation of 2 weeks’, 4 weeks’ and 6 weeks’ duration, respectively, and all were sacrificed at 136 days’ gestation (9 days pre-term). Nonoperated twins served as controls. The type II pneumocyte population was studied morphometrically using a combination of anti-surfactant protein B immunohistochemistry and computer-assisted stereologic morphometry at light and electron microscopic levels. Single-factor ANOVA was used for statistical analysis. Two weeks of tracheal ligation resulted in doubling of the total lung volume as a result of airspace distension and, to lesser extent, growth of the tissue compartment. With increasing duration of tracheal ligation, there was no additional lung growth. However, more prolonged tracheal occlusion was found to result in significant reduction of the surfactant system, as reflected in the marked decrease of total pneumocyte type II volume (3.14 cm3, 0.95 cm3, and 0.46 cm3, after 2, 4, and 6 weeks of ligation, compared with 5.96 cm3 for controls) and total pneumocyte type II number (13.9 × 109, 3.8 × 109, and 2.4 × 109, compared with 53.2 × 109 for controls). Ultrastructural analysis of the type II cells in obstructed lungs showed vacuolar degenerative changes that, after 6 weeks of ligation, were apparently irreversible. In utero tracheal ligation causes fetal lung hyperplasia, but results in reduction of and injury to the surfactant-producing cell population. Before tracheal occlusion can find widespread clinical application, its pathophysiology needs to be further elucidated.

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Received: 30 April 1997 / Accepted: 10 July 1997

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De Paepe, M., Papadakis, K., Johnson, B. et al. Fate of the type II pneumocyte following tracheal occlusion in utero: a time-course study in fetal sheep. Virchows Archiv 432, 7–16 (1998). https://doi.org/10.1007/s004280050128

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  • DOI: https://doi.org/10.1007/s004280050128

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