Intraluminal tracheal occlusion using a modified 8-mm Z-stent in a sheep model of left-sided congenital diaphragmatic hernia

J Matern Fetal Neonatal Med. 2012 Nov;25(11):2346-53. doi: 10.3109/14767058.2012.695825. Epub 2012 Jun 19.


Objective: 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).

Methods: 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.

Results: 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.

Conclusion: 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.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Female
  • Fetal Organ Maturity / physiology
  • Fetoscopy / methods*
  • Fetoscopy / veterinary
  • Functional Laterality
  • Gestational Age
  • Hernia, Diaphragmatic / pathology
  • Hernia, Diaphragmatic / surgery
  • Hernias, Diaphragmatic, Congenital*
  • Lung / cytology
  • Lung / embryology
  • Lung / pathology
  • Pregnancy
  • Sheep, Domestic
  • Stents*
  • Therapeutic Occlusion / methods*
  • Trachea / pathology
  • Trachea / surgery*