S. I. Al-Juboori1, E. Dobrinskikh2, M. Oria3, J. L. Peiro3, A. I. Marwan1 1University Of Colorado Denver,Division Of Pediatric Surgery/Department Of Surgery,Aurora, CO, USA 2University Of Colorado Denver,Department Of Medicine,Aurora, CO, USA 3University Of Cincinnati,Division Of Pediatric Surgery,Cincinnati, OH, USA
Introduction: Fetal Tracheal Occlusion (TO) is an experimental therapeutic approach to stimulate fetal lung development in the most severe Congenital Diaphragmatic Hernia (CDH) cases. Our laboratory has demonstrated a unique heterogeneous topological morphometric response of rabbit fetal lungs following 4 days of tracheal occlusion, namely: regions with control-like airspaces and others with enlarged airspaces. Currently, it is unknown whether TO in the setting of CDH will result in a similar heterogeneity. The aim of this study is to examine the heterogeneous fetal pulmonary parenchymal response following TO in the rabbit left-sided CDH model using morphometric analyses.
Methods: Fetal rabbits at 25 days gestation underwent surgical creation of left CDH followed by TO at 27 days and harvest on day 30. Lung-to-Body Weight Ratios (LBWRs) and their corresponding percent change relative to control counterparts, ΔLBWRs, were calculated for total lung weight, as well as left and right lung weights separately. In order to examine any heterogeneity in the pulmonary growth response in CDH model after TO, morphometric analyses, i.e., Tissue-to-Airspace Ratios (TARs), and the number and size of airspaces, were performed to evaluate parenchymal structural changes in control, CDH, and CDH+TO right and left lungs.
Results: Right and left lungs had a heterogeneous pulmonary growth response in CDH and after TO. The relative percent growth of the right lungs in CDH+TO was higher compared to the left lungs in the left-sided CDH model. Morphometric analyses revealed that right and left lungs were different at baseline and had heterogeneous TARs, in addition to size and number of airspaces within and between the lungs in the CDH and CDH+TO experimental groups. CDH right lungs had at least two distinct airspace populations, control-like, and larger TAR (smaller airspaces), unlike CDH left lungs where only one population was observed. TO resulted in the appearance of smaller TARs (enlarged airspaces) in both, right and left CDH+TO lungs. Furthermore, TARs were linearly and positively correlated with the number of airspaces in the pulmonary parenchyma of control, CDH, and CDH+TO animals. Whereas the number of airspaces and their respective average sizes exhibited an inverse nonlinear (exponential) relationship.
Conclusion: We demonstrated for the first time that morphometric response of CDH fetal lungs to tracheal occlusion is heterogeneous. Right and left lungs respond differently in percent growth and parenchymal structures. Parenchymal heterogeneity may result in variable functional response of the respiratory acini and therefore the unpredicted and variable clinical outcomes to this therapeutic intervention in hypoplastic lungs.
