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

PLoS One. 2017 Mar 30;12(3):e0174332. doi: 10.1371/journal.pone.0174332. eCollection 2017.

Abstract

Objectives: 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.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Hernia, Diaphragmatic / surgery*
  • Hernias, Diaphragmatic, Congenital / surgery*
  • Male
  • Rabbits
  • Wound Healing / physiology

Grants and funding

JDP is a Clinical Researcher of the Flanders Research Foundation (FWO Vlaanderen). LJ is a beneficiary of a NIH Wellcome Trust and Engineering and Physical Sciences Research Council (EPSRC) grant (GIFT-Surg project; WT101957 and NS/A000027/1). MPE and JvdM are funded with support of the Erasmus + Programme of the European Union (Framework Agreement number: 2013-0040). This publication reflects the views only of the author, and the Commission cannot be held responsible for any use which may be made of the information contained therein.