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- W2041168049 abstract "Background/Purpose: The treatment of severe tracheal stenosis/atresia remains essentially unresolved, particularly in the perinatal period. Previous models of these diseases have been restricted to adult animals. We sought to establish the principles of a large, surgical animal model of the congenital form of this spectrum of anomalies. Methods: Fetal lambs (n=8) underwent open surgery at 90-112 days gestation (term=145 days). Their cervical tracheas were encircled by a biocompatible polytetrafluoroethylene wrap, so as to extrinsically restrict their external diameter by 25%. Pregnancy was allowed to continue. Survivors (n=7) were killed at different time points post-operatively, namely 15, 21, 28, and 41days, before term. The manipulated tracheal segments were compared with their respective proximal portions, which served as controls. Analyses included morphometry, histology on H&E and Masson's trichrome stains, as well as quantitative extracellular matrix measurements of sulfated glycosaminoglycan, alpha-elastin, and total collagen contents. Statistical analyses were by the paired t-test and Pearson correlations, as appropriate (p<0.05). Results: At necropsy, the typical gross appearance of tracheal stenosis/atresia was present in all manipulated tracheal segments, along with hyper distended lungs, suggestive of upper airway obstruction. Histological findings were also characteristic of this disease spectrum, including the virtual disappearance of the membranous portion of the trachea, along with infolding, fragmentation, and/or posterior fusion of cartilaginous rings, often with disappearance of a discernible airway mucosa (figure). No inflammatory infiltrates were observed. There were significant decreases in diameter (p<0.001) and total collagen levels (p=0.005) on the manipulated trachea compared with the control portions. No significant differences were observed in overall elastin or glycosaminoglycan contents. Pearson correlations indicated that, over time, tracheal diameter decreased significantly on the experimental side (r=-0.87; p=0.01), but not on the control side (p=0.22). A significant time-dependent increase in elastin was noted on the control side (r=0.83; p=0.02), but not on the experimental side (p=0.27). Glycosaminoglycan content was stable on both the experimental and control portions. Collagen tended to increase with time on the control side (r=0.69; p=0.08), with no change on the experimental side (p=0.63). Conclusions: In a surgical ovine model, controlled extrinsic compression of the fetal trachea predictably leads to morphological and biochemical findings compatible with the congenital tracheal stenosis/atresia spectrum. This simple and easily reproducible prenatal model can be instrumental in the development of emerging therapies for these congenital anomalies." @default.
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- W2041168049 date "2010-02-01" @default.
- W2041168049 modified "2023-10-18" @default.
- W2041168049 title "A Fetal Model of the Tracheal Stenosis/Atresia Spectrum" @default.
- W2041168049 doi "https://doi.org/10.1016/j.jss.2009.11.301" @default.
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