Lewis Nicola A, Holm Bruce A, Rossman Jon, Swartz Daniel, Glick Philip L
Department of Surgery, Children's Hospital of Buffalo, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo, USA.
Pediatr Surg Int. 2011 Feb;27(2):119-24. doi: 10.1007/s00383-010-2790-3.
The lungs in congenital diaphragmatic hernia (CDH) are hypoplastic and immature making respiratory support one of the most challenging aspects of caring for these neonates. Vitamin A is essential for normal lung growth and development. It also promotes alveolarization. The aim of this study is to investigate the effects of antenatal vitamin A on lung growth and alveolarization and ventilation in the lamb model of CDH.
This study was approved by the Animal Care Committee of the State University of New York at Buffalo, and conforms to the National Institute of Health guidelines. Diaphragmatic defects were created at 79-81 days gestation. Group 1 lambs (CDH, n = 5) were untreated. In group 2 (CDH + vitamin A, n = 6) and group 3 lambs (control + vitamin A, n = 3) right jugular venous catheters were inserted at 118-120 days and retinyl palmitate (vitamin A) was administered until 135 days. The control group (n = 5) consisted of twin littermates. Lambs were delivered at 136-139 days and ventilated for 2 h according to a set protocol. The left lungs were harvested and fixed for histology.
Lung compliance was significantly higher in CDH + vitamin A (median 0.27, range 0.1-0.48 ml/cmH(2)O/kg) versus CDH lambs (median 0.07, range 0.07-0.18 ml/cmH(2)O/kg), P < 0.05. At 1 h CDH + vitamin A lambs experienced significantly lower PaCO(2) (median 115, range 35-194 mmHg vs. median 192, range 168-234 mmHg) and higher arterial pH (median 7.0, range 6.74-7.35 vs. median 6.73, range 6.5-6.81) than CDH lambs, P < 0.05. The lung weight to body weight ratio of CDH + vitamin A lambs was significantly less than that of CDH lambs (P < 0.05). Histology showed small thick walled air-spaces and no true alveoli in CDH lambs. In contrast, true alveoli and thinning of the inter-alveolar septums were seen in CDH + vitamin A lambs.
This is the first study to demonstrate an improvement in lung function and structural maturation when antenatal vitamin A is given in a surgical model of CDH.
先天性膈疝（CDH）患儿的肺发育不全且不成熟，这使得呼吸支持成为护理这些新生儿最具挑战性的方面之一。维生素A对正常肺的生长和发育至关重要。它还能促进肺泡化。本研究的目的是探讨产前维生素A对CDH羔羊模型肺生长、肺泡化及通气的影响。
本研究经纽约州立大学布法罗分校动物护理委员会批准，并符合美国国立卫生研究院的指南。在妊娠79 - 81天时制造膈疝缺损。第1组羔羊（CDH，n = 5）未接受治疗。在第2组（CDH + 维生素A，n = 6）和第3组羔羊（对照组 + 维生素A，n = 3）中，于118 - 120天时插入右颈静脉导管，并给予棕榈酸视黄酯（维生素A）直至135天。对照组（n = 5）由同窝双生羔羊组成。羔羊于136 - 139天时分娩，并按照既定方案通气2小时。取出左肺并固定用于组织学检查。
与CDH羔羊（中位数0.07，范围0.07 - 0.18 ml/cmH₂O/kg）相比，CDH + 维生素A组羔羊的肺顺应性显著更高（中位数0.27，范围0.1 - 0.48 ml/cmH₂O/kg），P < 0.05。在1小时时，CDH + 维生素A组羔羊的PaCO₂显著低于CDH羔羊（中位数115，范围35 - 194 mmHg，对比中位数192，范围168 - 234 mmHg），动脉血pH值更高（中位数7.0，范围6.74 - 7.35，对比中位数6.73，范围6.5 - 6.81），P < 0.05。CDH + 维生素A组羔羊的肺重量与体重之比显著低于CDH羔羊（P < 0.05）。组织学检查显示，CDH羔羊有小的厚壁气腔且无真正的肺泡。相比之下，CDH + 维生素A组羔羊可见真正的肺泡以及肺泡间隔变薄。
这是第一项表明在CDH手术模型中给予产前维生素A可改善肺功能和结构成熟度的研究。
