Effect of increased lung expansion on surfactant protein mRNA levels in lambs

Increased fetal lung expansion profoundly inhibits surfactant protein gene expression and stimulates cellular proliferation in the fetal lung. Our aim was to determine whether increased expansion of the lung after birth, by the application of a continuous positive airway pressure (CPAP) for 12 h, inhibits surfactant protein gene expression and stimulates cell division in lambs. Two week-old lambs were randomly divided into 2 groups (n = 5 for each), sedated, and exposed to either no CPAP (controls) or 10cmH₂O of CPAP during a 12-hour treatment period. After 2 h of the treatment, ³H-thymidine was administered to each lamb (iv) to measure pulmonary DNA synthesis rates over the following 10 h of treatment. To assess the increase in lung expansion, functional residual capacity (FRC) was measured before the start of the treatment period and again at 6 and 12 h. Compared with control lambs, a CPAP of 10 cmH₂O increased FRC from 26.8 ± 3.8 mL/kg to 62.9 ± 19.7 mL/kg at 6 h and it remained elevated at 12 h (56.2 ± 5.7 mL/kg). Despite this large increase in end expiratory lung volume (FRC), the mRNA levels for SP-A, SP-B, and SP-C and DNA synthesis rates in lung tissue were not altered. The results of this study indicate that, in contrast to the fetus, an increase in end expiratory lung volume of ∼100% does not affect surfactant protein gene expression or pulmonary DNA synthesis rates in 2 week old lambs. Thus, the response of the lung to increases in lung expansion varies markedly before and after birth.