Lung morphometry and collagen and elastin content: Changes during normal development and after prenatal hormone exposure in sheep

This study examined whether the improvement in lung function after prenatal hormone exposure coincided with changes in lung morphometry or in collagen and elastin content. Fetal lambs received a single intramuscular injection of betamethasone (0.5 mg/kg) plus L-thyroxine (T-4) (15 mu g/kg) or vehicl e control 48 h before delivery at 121, 128, or 135 d gestational age (d 121 , d 128, d 135, term = 150 d). T-4 was administered in conjunction with bet amethasone in an attempt to enhance the maturational response. The right-up per lobes were instillation fixed at 30 cm H2O by Karnovsky's fixative afte r a 40-min period of mechanical ventilation. A number of significant change s occurred between d 121 and d 135 in control animals: alveolar airspace vo lume increased by 270%; despite a 40% reduction in alveolar septal thicknes s, alveolar septal volume did not change appreciably, suggesting a "redistr ibution" of septal tissue into the formation of secondary alveolar septa, w hich doubled in number; and both parenchymal collagen and elastin volume in creased significantly, whereas pleural collagen and elastin volume did not change. In contrast to the changes seen in control animals, exposure to bet amethasone plus T-4 led to alveolar septal thinning at each gestational age without an associated increase in secondary septal number, a 40% decrease in alveolar septal volume, and a proportionate reduction in parenchymal ela stin at d 121. Although attenuation of alveolar septa coincides with redist ribution of septal tissue into the formation of secondary septa during norm al maturation, exposure to betamethasone plus T-4 promotes thinning of alve olar septa in the absence of secondary septal formation, which results in a loss of alveolar septal tissue.