Airway and vascular maturation stimulated by tracheal occlusion do not correlate in the rabbit model of diaphragmatic hernia

Abstract

Background:In animal models of congenital diaphragmatic hernia (CDH), tracheal occlusion (TO) has induced maturation of both airway spaces and vascular structures. Airway and vascular response to TO are assumed to occur in parallel. This study aims to describe and measure the relationship between airway and vascular maturation induced by TO. Methods: A rabbit model of CDH on gestational day (GD) 23 and TO on GD 28 (term = GD 31) has been used. Two study groups have been defined: DH (diaphragmatic hernia) and TO (DH treated with TO). Animals were collected on GD 30 and blood flow data of the pulmonary artery (pulsatility index (PI) and fractional moving blood volume) were ultrasonographically measured. Lung morphometry consisted of measurements of radial alveolar count (RAC) and arterial muscular thickness. results: Animals in the DH group (n = 9) had the worst hemodynamic parameters; their lungs were hypoplastic and had the thickest arterial muscular layer. Animals in the TO group (n = 10) had all these effects reversed. There were no correlations among hemodynamic, airway, and vascular parameters, except for RAC and PI (r = −0.528, P = 0.043). conclusion: Airway and vascular maturation after TO appear to be uncorrelated effects. TO could trigger several pathways that separately regulate airway and vascular responses.

The effects of tracheal occlusion on Wnt signaling in a rabbit model of congenital diaphragmatic hernia

“…Despite the benefits of the rabbit model of CDH, it has been under-utilized and remains outnumbered by nitrofen-induced rodent models of CDH due to increased cost and technical difficulty. Of the published rabbit CDH papers, only a few have studied the effects of TO, and to the best of our knowledge, none have studied the impact of CDH and potential rescue effects of TO on the Wnt signaling pathway [43,64,65] (Figure 20).…”

Fetal Tracheal Occlusion Increases Lung Basal Cells via Increased Yap Signaling

“…Pulmonary vascular pruning, vascular smooth muscle hypertrophy, and pulmonary hypertension are substantial problems for infants with CDH ( 2 ). In rabbit models of CDH and TO, TO enhanced lung perfusion ( 37 ) and reduced arterial wall thickness after surgical diaphragmatic hernia ( 38 ). The potential impact of TO in airway smooth muscle hypertrophy and lung fibroblast populations merits further investigation, which is now more achievable with mouse TO models.…”

“…We did not explore the impact of TO on mesenchymal or immune cells, although these signatures were more highly altered than that of Yap and basal cells. Of particular note, we did not deeply investigate or differentiate changes in gene expression that may have arisen from the pulmonary vasculature, which is known to be impacted by both CDH and TO ( 38 ). Finally, we could not obtain any lung tissues to directly assess basal cells in post-TO human lung, but we were able to secure a small number of specimens from infants with congenital occlusion of the trachea.…”

Murine Fetal Tracheal Occlusion Increases Lung Basal Cells via Increased Yap Signaling

“…Pulmonary vascular pruning, vascular smooth muscle hypertrophy, and pulmonary hypertension are substantial problems for infants with congenital diaphragmatic hernia (Coughlin et al, 2015). In rabbit models of CDH and TO, TO enhanced lung perfusion (Cruz-Martinez et al, 2009) and reduced arterial wall thickness after surgical DH (Prat Ortells et al, 2014). The potential impact of TO in airway smooth muscle hypertrophy and lung fibroblast populations merit further investigation which is now more achievable with mouse TO models.…”