In the rabbit model for DH, antenatal sildenafil rescues vascular branching and architecture, reduces pulmonary vascular resistances and also improves airway morphometry and respiratory mechanics.

We aimed to systematically review all published pre-clinical research on prenatal medical treatment of pulmonary hypoplasia in congenital diaphragmatic hernia (CDH). Background The neonatal mortality due to isolated CDH remains high. Whether fetal endoscopic tracheal occlusion (FETO) reduces mortality is still to be demonstrated. Therefore more potent preferentially medical therapy would be welcomed. Methods We searched MEDLINE (Pubmed), Embase and the Web of Science including all studies from the earliest date (1951) to December 2013. Article quality was assessed using the modified CAMRADES checklist. Inclusion criteria were those animal studies addressing prenatal medical interventions and principal variables were confirmation of a diaphragmatic defect, lung to body weight ratio (LBWR), formal airway morphometry or DNA/protein content. Results In total 983 articles were identified. Following abstract review, 96 articles were assessed by two authors in agreement with a third for eligibility. Of these, 43 were included in the final analysis. The median number of study quality checklist items (maximum 10) scored was 4 (IQ range: 2-5). Thirty (69.8%) of studies were in the nitrofen rat. The majority were treated with vitamins or glucocorticoids. Single studies reported some improvement in lung morphology with alternative therapies. It was impossible to identify a pattern in animal model selection or creation, mode, time point or duration of treatment and readouts. Only one study reported a sample size calculation. Conclusion Comparison in pre-clinical studies in CDH is challenging due to methodological variation. Agreed standardized methods need to be applied in future investigation of new medical therapies.

Gore-Tex® is a widely used durable patch for repair of congenital diaphragmatic defects yet may result in complications. We compared Gore-Tex with a composite of a radial pore-orientated collagen scaffold (RP-Composite) and clinically used porcine small intestinal submucosa (SIS; Surgisis®) in a rabbit model for diaphragmatic hernia. The growing rabbit mimics the rapid rib cage growth and reherniation rates seen in children. We created and immediately repaired left hemidiaphragmatic defects in 6-week-old rabbits with Gore-Tex, SIS, and an RP-Composite scaffold. An additional group of rabbits had a sham operation. At 90 days, survivors more than doubled in weight. We observed few reherniations or eventrations in Gore-Tex (17%) and RP-Composite (22%) implanted animals. However, SIS failed in all rabbits. Maximum transdiaphragmatic pressure was lower in Gore-Tex (71%) than RP-Composite implanted animals (112%) or sham (134%). Gore-Tex repairs were less compliant than RP-Composite, which behaved as sham diaphragm (p < 0.01). RP-Composite induced less foreign body giant cell reaction than Gore-Tex (p < 0.05) with more collagen deposition (p < 0.001), although there was a tendency for the scaffold to calcify. Unlike Gore-Tex, the compliance of diaphragms reconstructed with RP-Composite scaffolds were comparable with native diaphragm, whereas reherniation rates and transdiaphragmatic pressure measurements were similar.