Effects of tracheal occlusion with retinoic acid administration on normal lung development

Introduction Tracheal occlusion (TO) is an investigational therapy for severe congenital diaphragmatic hernia (CDH) that decreases pulmonary hypoplasia, but sustained TO also induces deficient surfactant synthesis. Intramuscular maternal administration of retinoic acid (RA) in a surgical rabbit model of CDH showed a beneficial effect on lung maturation. We evaluated the potential of RA delivery into the trachea and studied the combined effects of TO and RA on normal lung development. Methods Experiments were performed on normal rabbit fetuses. Liposomes and capric triglyceride (Miglyol®), alone and with RA, were administered in the trachea just before TO (d26). Lung morphology and surfactant production were studied at term (d30). Results TO increased lung weight and enhanced alveolar development but increased apoptotic activity and decreased surfactant expression. Tracheal injection of RA improved surfactant production to levels of normal controls. Conclusion We established the potential of liposome and Miglyol® as RA vehicle for delivering this bioactive molecule in the fetal airways. Tracheal RA injection seems to oppose the effects of TO in fetuses with normal lungs.