Improved pulmonary function in the nitrofen model of congenital diaphragmatic hernia
Link: http://www.ncbi.nlm.nih.gov/pubmed/27376883
Pediatr Res. 2016 Jul 20. doi: 10.1038/pr.2016.127. [Epub ahead of print]
Improved pulmonary function in the nitrofen model of congenital diaphragmatic hernia following prenatal maternal dexamethasone and/or sildenafil.
Burgos CM1,2, Pearson EG1, Davey M1, Riley J1, Jia H1, Laje P1, Flake AW1, Peranteau WH1.
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Abstract
BACKGROUND:
Pulmonary hypoplasia and hypertension is a leading cause of morbidity and mortality in congenital diaphragmatic hernia (CDH). The etiologic insult occurs early in gestation highlighting the potential of prenatal interventions. We evaluated prenatal pharmacologic therapies in the nitrofen CDH model.
METHODS:
Olive oil or nitrofen were administered alone or with dexamethasone (DM), sildenafil, or DM+sildenafil to pregnant rats. Newborn pups were assessed for lung function, structure and pulmonary artery (PA) flow and resistance.
RESULTS:
Prenatal DM treatment of CDH pups increased alveolar volume density (Vva), decreased interalveloar septal thickness, increased tidal volumes and improved ventilation without improving oxygenation or PA resistance. Sildenafil decreased PA resistance and improved oxygenation without improving ventilation or resulting in significant histologic changes. DM+sildenafil decreased PA resistance, improved oxygenation and ventilation while increasing Vva and decreasing interalveolar septal and pulmonary arteriole medial wall thickness. Lung and body weights were decreased in pups treated with DM and/or sildenafil.
CONCLUSION:
Prenatal DM or sildenafil treatment increased pulmonary compliance and decreased pulmonary vascular resistance respectively, and was associated with improved neonatal gas exchange but had a detrimental effect on lung and fetal growth. This study highlights the potential of individual and combined prenatal pharmacologic therapies for CDH management.Pediatric Research (2016); doi:10.1038/pr.2016.127.
Last update by RebeccaS (08-04-2016 03:52 PM)