Pulmonary alveolar and vascular morphometry after gel plug occlusion of the trachea in a fetal rabbit model of CDH

Purpose: Tracheal occlusion (TO) induces lung growth in congenital diaphragmatic hernia (CDH) but is also associated with drawbacks. We devised a temporary gel plug that induced lung growth when placed in the fetal trachea. This study evaluates the effects of temporary versus permanent TO on histologic radial alveolar count (RAC) and vascular morphometrics. Methods: Experimental CDH was created surgically in 64 New Zealand White rabbit fetuses on gestational day (GD) 24. On GD 27, these fetuses were randomized to intratracheal instillation of a fibrin gel plug (GP), tracheal suture ligation (SL), intratracheal instillation of normal saline (NS), or sham amniotomy (SH). Non-manipulated fetuses served as controls (NM). Histologic lung sections were assessed blindly for RAC and relative arterial adventitial thickness (%AT) as a variable for vascular remodelling. Results were statistically compared. Results: RAC was significantly lower in the ipsilateral lung of SH fetuses than in the contralateral lung (p=0.011). Mean RAC was higher after SL (p<0.001) and GP (p=0.03) compared to SH. Furthermore, %AT was higher in GP (50±28, p<0.001) and SL (45±26, p=0.003) fetuses than in controls (36±19). Conclusion: Temporary and permanent TO leads to increased RAC; this effect was more pronounced with permanent TO. Both interventions were associated with an increased %AT. These findings may explain the adverse clinical effects of TO, despite causing accelerated lung growth.