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 t he application of a continuous positive airway pressure (CPAP) for 12 h, in hibits surfactant protein gene expression and stimulates cell division in l ambs. Two week-old lambs were randomly divided into 2 groups (n = 5 for eac h), sedated, and exposed to either no CPAP (controls) or 10cmH(2)O Of CPAP during a 12-hour treatment period. After 2 h of the treatment, H-3-thymidin e was administered to each lamb (iv) to measure pulmonary DNA synthesis rat es over the following 10 h of treatment. To assess the increase in lung exp ansion, 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 cmH(2)O 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). Despi te 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 a ltered. The results of this study indicate that, in contrast to the fetus, an increase in end expiratory lung volume of similar to 100% does not affec t surfactant protein gene expression or pulmonary DNA synthesis rates in 2 week old lambs. Thus, the response of the lung to increases in lung expansi on varies markedly before and after birth.