Heterogeneous Response in Rabbit Fetal Diaphragmatic Hernia Lungs After Tracheal Occlusion

Area of Science:

• Fetal development
• Pulmonary research
• Surgical innovation

Background:

• Congenital diaphragmatic hernia (CDH) is a severe condition requiring therapeutic interventions.
• Fetal tracheal occlusion (TO) is an experimental approach to promote lung growth in severe CDH.
• Previous studies showed heterogeneous lung responses to TO in normal fetal lungs.

Purpose of the Study:

• To investigate the fetal lung response to TO in a left-sided CDH rabbit model.
• To analyze structural and metabolic changes in response to TO in CDH lungs.

Main Methods:

• Surgical creation of CDH followed by TO in fetal rabbits.
• Morphometric analysis, global metabolomics, and fluorescence lifetime imaging microscopy (FLIM) were employed.
• Evaluation of control, CDH, and CDH + TO lung groups.

Main Results:

• Significant baseline differences and heterogeneous growth responses were observed between right and left lungs in CDH and post-TO.
• Morphometry revealed variations in tissue-to-airspace ratios and airspaces.
• Metabolomics indicated slower metabolism in CDH lungs, with TO stimulating metabolic activity heterogeneously.
• FLIM showed localized heterogeneity in glycolysis, oxidative phosphorylation, and lipid-surfactant signals.

Conclusions:

• Tracheal occlusion induces a heterogeneous morphologic and metabolic response in both right and left fetal lungs within a left CDH rabbit model.
• These findings highlight the complex and localized effects of TO on lung development in CDH.