Kitano Yoshihiro, von Allmen Daniel, Kanai Masaki, Adzick N Scott, Flake Alan W
The Children's Institute for Surgical Science, The Children's Hospital of Philadelphia, Philadelphia, PA 19104-4399, USA.
Fetal Diagn Ther. 2003 Sep-Oct;18(5):333-7. doi: 10.1159/000071976.
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.
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.
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.
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.
尽管气管闭塞（TO）后肺生长的机制尚未完全明确，但肺液积聚是肺生长发生的必要条件。已知肾上腺素（Epi）、特布他林和利托君等β受体激动剂会抑制妊娠晚期胎儿肺液生成。我们假设在胎儿绵羊模型中，持续输注Epi会对TO后的肺生长产生不利影响。
20只胎羊分为四组。第1组：未行TO且未用Epi（n = 4）；第2组：行TO但未用Epi（n = 4）；第3组：未行TO但用Epi（n = 5），第4组：行TO且用Epi（n = 7）。在妊娠第130 - 134天（足月为145天）进行TO。在第3组和第4组中，在TO时通过皮下植入的微量渗透泵以2微克/分钟的速率向胎儿输注Epi。4天后处死胎儿，通过单因素方差分析比较四组之间的肺体积（LV，毫升/千克）、引流肺液（LF，毫升/千克）、湿肺重量/体重比（LW/BW，%）、每体重的右肺全干重比（dRLW/BW，克/千克）、肺实质体积密度（v(Vp)）以及右肺DNA和蛋白质含量。
第4组的LW/BW和dRLW/BW（3.91±0.52和2.10±0.28，均值±标准差）显著低于第2组（5.18±0.57和2.67±0.15），与第1组或第3组相比无统计学显著差异。LV、LF、V(Vp)以及DNA和蛋白质含量均呈现相似趋势。
向胎儿持续输注Epi会导致TO肺内液体积聚减少，并消除妊娠晚期胎儿绵羊TO后显著的肺生长。影响肺液分泌的药物可能对TO诱导的肺生长产生重大影响。
