Kitano Y, Flake A W, Quinn T M, Kanai M, Davies P, Sablich T J, Schneider C, Adzick N S, von Allmen D
Children's Institute for Surgical Science and The Center for Fetal Diagnosis and Treatment, The Children's Hospital of Philadelphia, PA, USA.
J Pediatr Surg. 2000 Feb;35(2):216-21; discussion 221-2. doi: 10.1016/s0022-3468(00)90012-5.
BACKGROUND/PURPOSE: Prenatal tracheal occlusion (TO) has been shown to accelerate lung growth, yet the mechanism for this effect is poorly understood. Increased intratracheal pressure (ITP) with accumulation of lung fluid and secondary airway distension (stretch) may provide a mechanical stimulus for growth. In this study, ITP after TO is measured continuously, and the effect of altering ITP on lung growth is examined.
Fetal lambs of 115 to 120 days of gestation (term, 145 days) underwent placement of an intratracheal catheter and an amniotic fluid reference catheter. First, ITP was monitored continuously in normal controls (n = 4) and in fetuses undergoing TO (n = 6). In a subsequent study, 2 groups of fetuses were compared. In the TO group (n = 5) ITP was monitored after TO. In the pressurized group (n = 5) ITP was maintained at 7 to 8 mm Hg by a continuous servo regulated pump that maintains a preset pressure by lactated Ringers infusion. The animals were killed after 4 days, and lung growth was compared.
In the control animals, ITP remained constant at 0.4 to 1.5 mm Hg. In the TO animals, ITP increased gradually during the initial 24 hours and plateaued at 4 to 5 mm Hg. In the second set of animals, ITP in the pressurized group was maintained at approximately 8 mm Hg using the infusion system. Lung volume (135.7+/-17.4 v. 95.2+/-14.8 mL/kg; P<.01), lung weight to body weight (6.70+/-0.73 v. 5.33+/-0.77%; P<.05), whole right lung dry weight (3.10+/-0.22 v. 2.63+/-0.20 mg/kg; P<.05), and right lung DNA and protein contents (87.3+/-6.0 v. 74.6+/-8.1 mg/kg, 2,310+/-248 v. 1,860+/-196 mg/kg, respectively; P<.05) were increased significantly in the pressurized group compared with the TO group. Morphometry confirmed greater volume of respiratory region and increased alveolar surface area in the pressurized lung.
TO results in a gradual increase in ITP over 15 to 24 hours, which plateaus at 4 to 5 mm Hg. Further increasing ITP by infusion of crystalloid significantly augments lung growth beyond that observed with TO alone. These data support the hypothesis that airway pressure and secondary mechanical stretch are the primary stimuli of TO induced lung growth.
背景/目的：产前气管阻塞（TO）已被证明可加速肺生长，但其作用机制尚不清楚。气管内压力（ITP）升高伴肺液积聚和继发性气道扩张（拉伸）可能为生长提供机械刺激。在本研究中，连续测量TO后的ITP，并研究改变ITP对肺生长的影响。
对妊娠115至120天（足月为145天）的胎羊进行气管内导管和羊水参考导管置入。首先，在正常对照组（n = 4）和接受TO的胎儿（n = 6）中连续监测ITP。在随后的研究中，比较了2组胎儿。TO组（n = 5）在TO后监测ITP。加压组（n = 5）通过连续伺服调节泵将ITP维持在7至8 mmHg，该泵通过输注乳酸林格液维持预设压力。4天后处死动物，比较肺生长情况。
在对照动物中，ITP保持在0.4至1.5 mmHg恒定。在接受TO的动物中，ITP在最初24小时内逐渐升高，在4至5 mmHg达到平台期。在第二组动物中，使用输注系统将加压组的ITP维持在约8 mmHg。与TO组相比，加压组的肺体积（135.7±17.4对95.2±14.8 mL/kg；P<0.01）、肺重量与体重之比（6.70±0.73对5.33±0.77%；P<0.05）、整个右肺干重（3.10±0.22对2.63±0.20 mg/kg；P<0.05）以及右肺DNA和蛋白质含量（分别为87.3±6.0对74.6±8.1 mg/kg、2310±248对1860±196 mg/kg；P<0.05）显著增加。形态计量学证实加压肺的呼吸区域体积更大，肺泡表面积增加。
TO导致ITP在15至24小时内逐渐升高，在4至5 mmHg达到平台期。通过输注晶体液进一步增加ITP可显著增强肺生长，超过单独TO所观察到的情况。这些数据支持气道压力和继发性机械拉伸是TO诱导肺生长的主要刺激因素这一假说。
