ArticleWorld journal of pediatrics : WJP2014
Antenatal use of bosentan and/or sildenafil attenuates pulmonary features in rats with congenital diaphragmatic hernia.
Article in World journal of pediatrics : WJP, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 29 citations in OpenAlex.
- Antenatal Sildenafil for Congenital Diaphragmatic Hernia: A Systematic Review and Bayesian Meta-Analysis of Preclinical Studies.Biomedicines · 2025Review
- Infants With a Congenital Diaphragmatic Hernia Had Favourable Pulmonary Hypertension Outcomes at 1 Year of Age.Acta paediatrica (Oslo, Norway : 1992) · 2025Article
- Congenital diaphragmatic hernia: phosphodiesterase-5 and Arginase inhibitors prevent pulmonary vascular hypoplasia in rat lungs.Pediatric research · 2024Article
- Long-term follow-up of patients with congenital diaphragmatic hernia.World journal of pediatric surgery · 2024Review
- Emerging antenatal therapies for congenital diaphragmatic hernia-induced pulmonary hypertension in preclinical models.Pediatric research · 2021Review
- Pulmonary vascular development in congenital diaphragmatic hernia.European respiratory review : an official journal of the European Respiratory Society · 2018Review
- Congenital diaphragmatic hernias: from genes to mechanisms to therapies.Disease models & mechanisms · 2017Review
- Improved pulmonary function in the nitrofen model of congenital diaphragmatic hernia following prenatal maternal dexamethasone and/or sildenafil.Pediatric research · 2016Article
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8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLung hypoplasia, pulmonary persistent hypertension of the newborn and its morphological changes are the main features in congenital diaphragmatic hernia (CDH). This study was undertaken to investigate if antenatal use of sildenafil and/or bosentan attenuates vascular remodeling, promotes branching, and improves alveolarization in experimental nitrofeninduced CDH.
methodsNitrofen (100 mg) was gavage-fed to pregnant rats at post conception day (PCD) 9 to induce CDH. The rats were randomized to 5 groups: 1) control; 2) nitrofen; 3) nitrofen+sildenafil 100 mg/kg per day at PCD 16-20; 4) nitrofen+bosentan 30 mg/kg per day, at PCD 16-20, and 5) nitrofen+bosentan+sildenafil, same doses and administration days. After cesarean delivery, the offsprings were sacrificed. The diaphragmatic defect and pulmonary hypoplasia were identified, and the lungs were dissected. Arterial wall thickness, bronchiolar density and alveolarization were assessed.
resultsThe offsprings with CDH were characterized by severe pulmonary hypoplasia (lung weight-to-body weight ratio: 0.0263 [95% confidence interval (CI) 0.0242-0.0278)] in the nitrofen group versus 0.0385 (95% CI 0.0355-0.0424) in the control group (P=0.0001). Pulmonary arterial wall thickness was decreased to 3.0 (95% CI 2.8-3.7) μm in the nitrofen+sildenafil group versus 5.0 (95% CI 4.1-4.9) μm in the nitrofen group (P=0.02). Terminal bronchioles increased to 13.7 (95% CI 10.7-15.2) μm in the nitrofen+bosentan group in contrast to 8.7 (95% CI 7.2-9.4) μm in the nitrofen group (P=0.002). More significant differences (P=0.0001) were seen in terminal bronchioles in the nitrofen+sildenafil+bosentan group than in the nitrofen group [14.0 (95% CI 12.5-15.4) μm versus 8.5 (95% CI 7.1-9.3) μm]. Pulmonary arterial wall thickness was also decreased in the former group.
conclusionsIn this rat model, antenatal treatment with sildenafil attenuates vascular remodeling. Bosentan promotes the development of terminal bronchioles in nitrofen-induced CDH.
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