title: A growing animal model for neonatal repair of large diaphragmatic defects to evaluate patch function and outcome.
abstract: OBJECTIVE
  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.
  
  
  BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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<0.05). Patched animals had a compensatory increase in their right hemi-diaphragmatic fiber cross-sectional area (p<0.0001).
  
  
  CONCLUSIONS
  A primarily patched 3*3cm defect in growing rabbits, under laryngeal mask airway ventilation, enables adequate survival with normal lung function and reduced maximum transdiaphragmatic pressure compared to controls.
authors.affiliation: Department of Development and Regeneration, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Mary Patrice
authors.identifier: http://orcid.org/0000-0002-6437-8972
authors.initials: MP
authors.lastname: Eastwood
authors.affiliation: Department of Development and Regeneration, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Luc
authors.initials: L
authors.lastname: Joyeux
authors.affiliation: Department of Development and Regeneration, Katholieke Universiteit Leuven, Leuven, Belgium.|Department of Obstetrics and Gynaecology, Prince of Songkla University, Hat Yai, Thailand.
authors.forename: Savitree
authors.initials: S
authors.lastname: Pranpanus
authors.affiliation: Department of Development and Regeneration, Katholieke Universiteit Leuven, Leuven, Belgium.|Clinical department of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Johannes
authors.initials: J
authors.lastname: Van der Merwe
authors.affiliation: Department of Pathology, Group Biomedical Sciences, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Eric
authors.initials: E
authors.lastname: Verbeken
authors.affiliation: Laboratory Animal Center, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Stephanie
authors.initials: S
authors.lastname: De Vleeschauwer
authors.affiliation: Laboratory of Pneumology, Katholieke Universiteit Leuven, Leuven. Belgium.
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Gayan-Ramirez
authors.affiliation: Department of Development and Regeneration, Katholieke Universiteit Leuven, Leuven, Belgium.|Clinical department of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Deprest
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006548:Hernia, Diaphragmatic / Q000601:surgery*; D065630:Hernias, Diaphragmatic, Congenital / Q000601:surgery*; D008297:Male; D011817:Rabbits; D014945:Wound Healing / Q000502:physiology