title: Improved pulmonary function in the nitrofen model of congenital diaphragmatic hernia following prenatal maternal dexamethasone and/or sildenafil.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: The Center for Fetal Research, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.|Department for Women's and Children's Health, Division of Pediatric Surgery, Karolinska Institute, Stockholm, Sweden.
authors.forename: Carmen Mesas
authors.initials: CM
authors.lastname: Burgos
authors.affiliation: The Center for Fetal Research, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Erik G
authors.initials: EG
authors.lastname: Pearson
authors.affiliation: The Center for Fetal Research, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Marcus
authors.initials: M
authors.lastname: Davey
authors.affiliation: The Center for Fetal Research, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: John
authors.initials: J
authors.lastname: Riley
authors.affiliation: The Center for Fetal Research, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Huimin
authors.initials: H
authors.lastname: Jia
authors.affiliation: The Center for Fetal Research, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Pablo
authors.initials: P
authors.lastname: Laje
authors.affiliation: The Center for Fetal Research, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Alan W
authors.initials: AW
authors.lastname: Flake
authors.affiliation: The Center for Fetal Research, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: William H
authors.initials: WH
authors.lastname: Peranteau
mesh_terms: D000818:Animals; D001160:Arterioles / Q000503:physiopathology; D001835:Body Weight; D003907:Dexamethasone / Q000008:administration & dosage*; D005260:Female; D065630:Hernias, Diaphragmatic, Congenital / Q000139:chemically induced / Q000188:drug therapy*; D006976:Hypertension, Pulmonary / Q000188:drug therapy; D008168:Lung / Q000098:blood supply* / Q000187:drug effects; D000069463:Olive Oil / Q000737:chemistry; D009929:Organ Size / Q000187:drug effects; D010100:Oxygen / Q000737:chemistry; D010647:Phenyl Ethers / Q000009:adverse effects; D011247:Pregnancy; D011270:Pregnancy, Animal; D011651:Pulmonary Artery / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012129:Respiratory Function Tests; D012143:Respiratory Physiological Phenomena; D000068677:Sildenafil Citrate / Q000008:administration & dosage*; D013318:Stroke Volume; D014132:Trachea / Q000187:drug effects
chemical_list: D000069463:Olive Oil; D010647:Phenyl Ethers; D003907:Dexamethasone; D000068677:Sildenafil Citrate; C007350:nitrofen; D010100:Oxygen