A Large Animal Model of the Fetal Tracheal Stenosis/Atresia Spectrum

• Published in: The Journal of surgical research 2011-11, Vol.171 (1), p.164-169
• Main Authors: Turner, Christopher G.B., M.D, Klein, Justin D., M.D, Ahmed, Azra, B.S, Zurakowski, David, Ph.D, Fauza, Dario O., M.D
• Format: Article
• Language: English
• Subjects: Animals; Biocompatible Materials; Biological and medical sciences; Chronic obstructive pulmonary disease, asthma; Collagen - metabolism; Disease Models, Animal; Elastin - metabolism; Extracellular Matrix - metabolism; Extracellular Matrix - pathology; Female; Fetus - surgery; Fluorocarbon Polymers; General aspects; Medical sciences; Organogenesis; Pneumology; Pregnancy; Sheep; Surgery; Trachea - abnormalities; Trachea - pathology; Tracheal Stenosis - pathology
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2010.02.037

Background Treatment of congenital tracheal stenosis/atresia remains essentially unresolved. Previous models of this disease entity have been restricted to rodents and the chick. We sought to establish the principles of a large, surgical animal model of this spectrum of fetal anomalies. Methods Fetal lambs (n = 8) underwent open surgery at 90-112 days gestation. Their cervical tracheas were encircled by a biocompatible polytetrafluoroethylene wrap, so as to extrinsically restrict their external diameter by 25%. Survivors (n = 7) were killed at different time points post-operatively before term. The manipulated tracheal segments were compared with their respective proximal portions (controls). Analyses included morphometry, histology and quantitative extracellular matrix measurements. Results At necropsy, the typical gross appearance of tracheal stenosis/atresia was present in all manipulated tracheal segments. Histological findings included 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 the airway mucosa. 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. A significant time-dependent increase in elastin was noted on the control, but not the experimental side. Conclusions In a surgical ovine model, controlled extrinsic compression of the fetal trachea 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.