A growing animal model for neonatal repair of large diaphragmatic defects to evaluate patch function and outcome

• Published in: PloS one 2017-03, Vol.12 (3), p.e0174332-e0174332
• Main Authors: Eastwood, Mary Patrice, Joyeux, Luc, Pranpanus, Savitree, Van der Merwe, Johannes, Verbeken, Eric, De Vleeschauwer, Stephanie, Gayan-Ramirez, Ghislaine, Deprest, Jan
• Format: Article
• Language: English
• Subjects: Animal models; Animal research models; Animals; Biology and Life Sciences; Breathing; Care and treatment; Complications; Congenital diseases; Defects; Diaphragms; Disease Models, Animal; Genetic disorders; Grafts; Hernia; Hernia, Diaphragmatic - surgery; Hernias; Hernias, Diaphragmatic, Congenital - surgery; Histology; Intubation; Lungs; Male; Mechanical ventilation; Medicine and Health Sciences; Neonates; Newborn babies; Pressure; Rabbits; Research and Analysis Methods; Respiration; Respiratory failure; Respiratory function; Respiratory tract; Scoliosis; Stricture; Surgical outcomes; Survival; Test procedures; Thoracic surgery; Ventilation; Wound Healing - physiology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0174332

We aimed to develop a more representative model for neonatal congenital diaphragmatic hernia repair in a large animal model, by creating a large defect in a fast-growing pup, using functional pulmonary and diaphragmatic read outs. Grafts are increasingly used to repair congenital diaphragmatic hernia with the risk of local complications. Growing animal models have been used to test novel materials. 6-week-old rabbits underwent fiberoptic intubation, left subcostal laparotomy and hemi-diaphragmatic excision (either nearly complete (n = 13) or 3*3cm (n = 9)) and primary closure (Gore-Tex patch). Survival was further increased by moving to laryngeal mask airway ventilation (n = 15). Sham operated animals were used as controls (n = 6). Survivors (90 days) underwent chest X-Ray (scoliosis), measurements of maximum transdiaphragmatic pressure and breathing pattern (tidal volume, Pdi). Rates of herniation, lung histology and right hemi-diaphragmatic fiber cross-sectional area was measured. Rabbits surviving 90 days doubled their weight. Only one (8%) with a complete defect survived to 90 days. In the 3*3cm defect group all survived to 48 hours, however seven (78%) died later (16-49 days) from respiratory failure secondary to tracheal stricture formation. Use of a laryngeal mask airway doubled 90-day survival, one pup displaying herniation (17%). Cobb angel measurements, breathing pattern, and lung histology were comparable to sham. Under exertion, sham animals increased their maximum transdiaphragmatic pressure 134% compared to a 71% increase in patched animals (p