Lipsett J, Cool J C, Runciman S I, Ford W D, Kennedy J D, Martin A J
Department of Histopathology, Child Health Research Institute, Women's and Children's Hospital, Adelaide, North Adelaide, South Australia, Australia.
Pediatr Pulmonol. 1998 Apr;25(4):257-69. doi: 10.1002/(sici)1099-0496(199804)25:4<257::aid-ppul6>3.0.co;2-h.
The incidence of congenital diaphragmatic hernia (CDH) is 1:1,207-5,000, and the condition is associated with high mortality and morbidity, attributed principally to associated pulmonary hypoplasia. Repairing the diaphragmatic defect by antenatal surgery has high mortality, mainly due to premature labor. Antenatal tracheal occlusion, which is achievable by less invasive methods, stimulates lung growth (weight and DNA). However, its effectiveness in reversing structural and maturational abnormalities and its optimal timing requires further investigation. We hypothesized that (1) antenatal tracheal occlusion performed in the lamb model of congenital diaphragmatic hernia will stimulate lung growth and structural development and restore lung structure and maturity toward normal levels by term gestation; (2) effects will be detectable by morphometric measurements of the following parameters: lung volume, ratio of parenchyma to nonparenchyma, volume density of connective tissue within nonparenchyma, ratio of gas exchange tissue to airspace in parenchyma, gas exchange surface area, capillary loading, alveolar/airspace density and alveolar perimeter; (3) effects will be seen in all lobes of the lung; and (4) a greater effect will be observed when tracheal occlusion is performed early rather than late in gestation. Fourteen lambs underwent CDH creation at gestation day 72-74 followed by tracheal occlusion at day 101 (n = 7) or 129 (n = 7). They were delivered by Cesarean section at 143 days (term = 145-149). Lungs were obtained at autopsy, inflation fixed, divided into lobes, and sampled; morphometric analysis was performed. Comparisons were made with previously reported results from control lungs of normal lambs and lambs with untreated CDH. In comparison with untreated lungs, antenatal tracheal occlusion at both times resulted in increased volumes for total lung and lobes, increased volume density of parenchyma and of airspace within parenchyma, and increased gas exchange surface areas. Normal values for gas exchange surface area density, and alveolar density and perimeter were attained and the lungs appeared more mature than non-occluded lungs. Tracheal occlusion earlier in gestation produced a greater effect, achieving greater than normal values for lung volumes and volume densities, whereas the capillary loading value was similar to normal lung. Later occlusion achieved less than normal values for lung volumes and volume densities, with a reduced capillary loading value. We conclude that antenatal tracheal occlusion is capable of reversing structural total lung and lobar hypoplasia and immaturity caused by CDH as determined by morphometrically determined parameters. The effect is greater when tracheal occlusion is performed early rather than late in gestation. The results are encouraging for development of treatment methods for humans with antenatally diagnosed CDH.
先天性膈疝（CDH）的发病率为1:1207至1:5000，该病症与高死亡率和高发病率相关，主要归因于相关的肺发育不全。通过产前手术修复膈肌缺损死亡率很高，主要原因是早产。产前气管阻塞可以通过侵入性较小的方法实现，能刺激肺生长（重量和DNA）。然而，其在逆转结构和成熟异常方面的有效性及其最佳时机需要进一步研究。我们假设：（1）在先天性膈疝羔羊模型中进行的产前气管阻塞将刺激肺生长和结构发育，并在足月妊娠时使肺结构和成熟度恢复到正常水平；（2）通过对以下参数的形态测量可以检测到效果：肺体积、实质与非实质的比例、非实质内结缔组织的体积密度、实质内气体交换组织与气腔的比例、气体交换表面积、毛细血管负荷、肺泡/气腔密度和肺泡周长；（3）在肺的所有叶中都能看到效果；（4）在妊娠早期而不是晚期进行气管阻塞会观察到更大的效果。14只羔羊在妊娠第72 - 74天制造CDH，然后在第101天（n = 7）或第129天（n = 7）进行气管阻塞。它们在143天通过剖宫产分娩（足月为145 - 149天）。在尸检时获取肺，充气固定，分成叶并取样；进行形态分析。与先前报道的正常羔羊和未治疗CDH羔羊的对照肺结果进行比较。与未治疗的肺相比，两次产前气管阻塞均导致全肺和各叶体积增加，实质和实质内气腔的体积密度增加，以及气体交换表面积增加。达到了气体交换表面积密度、肺泡密度和周长的正常值，并且肺看起来比未阻塞的肺更成熟。妊娠早期进行气管阻塞产生的效果更大，肺体积和体积密度达到高于正常值，而毛细血管负荷值与正常肺相似。后期阻塞的肺体积和体积密度低于正常值，毛细血管负荷值降低。我们得出结论，产前气管阻塞能够逆转由CDH引起的全肺和肺叶结构发育不全和不成熟，这由形态测量确定的参数所决定。在妊娠早期而不是晚期进行气管阻塞效果更大。这些结果对于开发产前诊断为CDH的人类治疗方法是令人鼓舞的。
