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

Abstract

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.

Keywords::

• Congenital diaphragmatic hernia
• CDH
• fetal surgery
• fetoscopy
• tracheal occlusion

Acknowledgments

We would like to thank Dr. Scott Nelson for his invaluable contribution regarding the methodology of this investigation, the fellows of the Maternal-Fetal Medicine Division of the Hospital Universitario Universidad Central de Venezuela for their assistance in the surgeries, and the support, assistance and collaboration of the Venezuelan Institute for Scientific Investigation (IVIC) including Dr. Egidio Romano and Dr. Mercedes Fernández from the Department of Experimental Medicine, Dr. FulgencioProverbio and Dr. Reinaldo Marín from the Biophysics and Biochemistry Department, and Dr. Ernesto Candela from the vivarium. We would like to take this opportunity to thank Cook Ob/Gyn Inc. for providing the Z-stents and Richard Wolf Inc. for their technical support. Finally, our immense gratitude to the Venezuelan National Council for Science and Technology, CONICIT, for the partial funding of this project.

Declaration of Interest: This work was performed at IVIC and was partially funded by the Venezuelan National Council for Science and Technology, CONICIT, grant number S1-98003169.