Sosa-Sosa Christian, Bermúdez Carlos, Chmait Ramen H, Kontopoulos Eftichia, Córdoba Yvette, Guevara-Zuloaga Freddy, Steffensen Thora, Quintero Rubén A
Instituto Venezolano de Investigaciones Científicas (IVIC), Altos de Pipe, Estado Miranda, Venezuela.
J Matern Fetal Neonatal Med. 2012 Nov;25(11):2346-53. doi: 10.3109/14767058.2012.695825. Epub 2012 Jun 19.
To evaluate pulmonary growth and development after fetoscopic intraluminal tracheal occlusion (FITO) using a modified 8-mm Z-stent in an ovine model of congenital left-sided diaphragmatic hernia (CDH).
Thirty-three time-dated ewes were studied: Group I: healthy controls; Group II: CDH controls (untreated); Group III: CDH treated with FITO. CDH was created in Groups II and III at 70-80 days' gestation. FITO was performed at 100-110 days. Left lung histological, morphometric, immunohistochemical and biochemical studies were conducted after delivery and euthanasia at 138 days.
Fifteen (45%) animals (Group I: 3; Group II: 5; Group III: 7) were available for analysis. The left lung parenchymal volume to fetal weight ratios were similar between Groups I and III (p = 0.24), and higher than Group II (p < 0.05III (79 versus 75%, p = 0.26), compared to 41% in Group II (p < 0.05). Pulmonary hypoplasia occurred in 1/7 (16%) in the FITO group, compared to 100% in Group II and 0% in Group I (p = .003). DNA and protein were significantly increased in Group III (p < 0.001). The concentration of type II pneumocytes was similar between healthy controls and the FITO group, and was paradoxically increased in untreated hernia fetuses. There was no histological evidence of tracheal injury.
FITO with a modified 8-mm Z-stent is associated with lung growth and maturation similar to controls without obvious deleterious effects. A phase I clinical trial of FITO with the modified 8-mm Z-stent in severe CDH patients seems warranted.
在先天性左侧膈疝(CDH)的绵羊模型中,使用改良的8毫米Z形支架评估胎儿镜腔内气管阻塞(FITO)后肺的生长和发育情况。
对33只定时受孕的母羊进行研究:第一组:健康对照组;第二组:CDH对照组(未治疗);第三组:接受FITO治疗的CDH组。在妊娠70 - 80天时,对第二组和第三组造成CDH。在100 - 110天时进行FITO。在138天时分娩并实施安乐死后,对左肺进行组织学、形态计量学、免疫组织化学和生化研究。
15只(45%)动物(第一组:3只;第二组:5只;第三组:7只)可供分析。第一组和第三组的左肺实质体积与胎儿体重之比相似(p = 0.24),且高于第二组(p < 0.05)。第三组的肺实质占比为79%,与第一组(75%,p = 0.26)相近,而第二组为41%(p < 0.05)。FITO组中1/7(16%)发生肺发育不全,相比之下,第二组为100%,第一组为0%(p = 0.003)。第三组的DNA和蛋白质显著增加(p < 0.001)。健康对照组和FITO组之间II型肺细胞的浓度相似,而在未治疗的疝胎儿中反而增加。没有气管损伤的组织学证据。
使用改良的8毫米Z形支架进行FITO与肺的生长和成熟相关,类似于对照组,且无明显有害影响。对严重CDH患者进行改良8毫米Z形支架FITO的I期临床试验似乎是必要的。