Abstract 1810 Neonatal Pulmonology I: Mechanical Influences on Lung Development Platform, Tuesday, 5/4

Occlusion of the fetal trachea has been shown to accelerate lung growth in sheep, rabbit and rat models. However, studies in sheep indicate that TO inhibits type 2 cell numbers, lamellar bodies per type 2 cell, and surfactant proteins and lipid composition. We hypothesized that TO of normal rat lungs would impair type 2 cell proliferation and maturation of the surfactant system. TO was performed on 4-5 randomly chosen fetuses of time-dated pregnant Sprague-Dawley rats on fetal day 19 (canalicular stage of lung development). We have recently reported significant lung growth in this model as indicated by wet lung to body weight ratio (TO 6.34±0.26% vs Control 2.64±0.72%, p<0.01; mean±sem), lung dry weight (TO 17.4±0.59mg, Control 12.1±0.43mg, p<0.01), total protein (TO 14.3±1.7mg vs Control 8.7±0.46mg, p<0.01), and DNA content (TO 1210±87µg vs Control 828±39µg, p<0.01) [J Pediatr Surg 33(12):1741-1744, 1998]. Fetuses were sacrificed on 21.5 days gestation (term = 22 d) for comparison of type 2 cells and surfactant proteins using Western blotting and immunohistochemistry (TO n=5-7; Control n=7-9 fetuses, 7 litters). There were no significant differences in SP-A and SP-B levels by Western-blotting of lung homogenates from TO and Control lungs (SP-A: TO 6191±370 vs Control 5027±473, p=0.08; SP-B: TO 2637±758 vs Control 3541±578, p=0.36; mean densitometry units;sem). There were no significant differences between sham operated and control fetuses. This was confirmed by immunohistochemistry using antibodies for SP-A, B, and NPro-SP-C, which showed similar staining intensity of type 2 cells in both the TO and Control lungs. Inflation fixed lungs (10 cmH2O, TO n=5, Control n=5, 12 randomly chosen type 2 cells per animal) were further studied by transmission electron microscopy. Similar numbers of intracellular mature lamellar bodies (TO 5.8±0.9 vs Control 6.5±1.0, p=0.61; mean±sem) and glycogen lakes (graded 0-3+; TO 1.7±0.04 vs Control 1.7±0.2, p=0.93; mean±sem) per type 2 cell were observed. There was a small but significant reduction in the number of type 2 cells per alveolus in the TO group (TO 0.86±0.16 vs Control 1.42±0.14, p=0.03; mean±sem). We conclude that TO of normal fetal lungs with retention of fetal lung fluid impairs type 2 cell proliferation but does not impact on the expression of surfactant proteins A, B, and C. Developmental stage at and duration of TO are likely to be crucial factors in balancing the effects of TO on lung growth versus maturation.