Epinephrine inhibits tracheal occlusion induced lung growth in fetal sheep

Objective: Although the mechanisms responsible for lung growth following tracheal occlusion (TO) are not fully understood, lung fluid accumulation is a requirement for growth to occur. It is known that betamimetics such as epinephrine (Epi), terbutaline, and ritodrine inhibit fetal lung fluid production late in gestation. We hypothesized that continuous infusion of Epi would have a detrimental effect on lung growth following TO in the fetal sheep model.

Methods: Twenty fetal lambs were divided into four groups. Group 1: no TO without Epi (n = 4); group 2: TO without Epi (n = 4); group 3: no TO with Epi (n = 5), and group 4: TO with Epi (n = 7). TO was performed on days 130-134 of gestation (full term = 145 days). In groups 3 and 4, Epi was infused into the fetus at a rate of 2 microg/min using a miniosmotic pump implanted subcutaneously at the time of TO. The fetuses were sacrificed after 4 days, and lung volume (LV, ml/kg), drained lung fluid (LF, ml/kg), wet lung weight/body weight ratio (LW/BW, %), whole right-lung dry weight per body weight ratio (dRLW/BW, g/kg), volume density of lung parenchyma (v(Vp)), and right-lung DNA and protein contents were compared among the four groups by one-way Anova.

Results: LW/BW and dRLW/BW of group 4 (3.91 +/- 0.52 and 2.10 +/- 0.28, mean +/- SD) were significantly lower than those of group 2 (5.18 +/- 0.57 and 2.67 +/- 0.15) and were not statistically significantly different from those of group 1 or 3. LV, LF, V(Vp), and DNA and protein contents all showed a similar trend.

Conclusions: Continuous infusion of Epi to the fetus results in less fluid accumulation within the TO lungs and abolishes significant lung growth after TO in the late-gestation fetal lamb. Drugs affecting lung fluid secretion may have a major impact on TO-induced lung growth.