title: Combined antenatal therapy with retinoic acid and tracheal occlusion in a rat model of congenital diaphragmatic hernia.
abstract: OBJECTIVE
  To investigate the effect of combined prenatal treatment with retinoic acid (RA) and tracheal occlusion (TO) on the pulmonary vascular morphology and expression of vascular endothelial growth factors (VEGF) and its receptors in a rat model of congenital diaphragmatic hernia (CDH).
  
  
  METHODS
  Rats were given nitrofen at 9 days of gestation followed by no treatment (CDH), RA (CDH + RA), TO (CDH + TO), or both (CDH + RA + TO) (n = 16). We measured the median wall thickness of the pulmonary arterioles (MWT) and analyzed the expression of VEGF and its receptors (VEGFR1 and VEGFR2).
  
  
  RESULTS
  Compared to control animals, CDH had increased MWT (44 ± 15 vs. 58 ± 7; p < 0.05) and decreased expression of VEGF, VEGFR1, and VEGFR2 (p < 0.05). Treatment with RA or TO alone, and RA + TO reduced the MWT (46 ± 9, 42 ± 11, 46 ± 8, respectively) and improved the expression of VEGF, VEGFR1, and VEGFR2 compared to CDH (p < 0.05). However, the combination of RA + TO did not confer additional benefit in the reduction of the MWT or in increasing the VEGF and its receptors compared to either treatment alone.
  
  
  CONCLUSIONS
  Antenatal treatment with either RA or TO improved the MWT and expression of VEGF and its receptors in a CDH rat model. However, combined treatment with RA + TO was not superior to either treatment alone.
authors.affiliation: Division of Neonatology and Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Augusto Frederico
authors.initials: AF
authors.lastname: Schmidt
authors.affiliation: Laboratory of Experimental Fetal Surgery, Division of Pediatric Surgery, Department of Surgery and Anatomy, Ribeirao Preto Medical School, University of Sao Paulo, Av. Bandeirantes, 3900, Ribeirao Preto, SP, CEP: 14048-900, Brazil.
authors.forename: Frances Lilian Lanhellas
authors.initials: FL
authors.lastname: Gonçalves
authors.affiliation: Laboratory of Experimental Fetal Surgery, Division of Pediatric Surgery, Department of Surgery and Anatomy, Ribeirao Preto Medical School, University of Sao Paulo, Av. Bandeirantes, 3900, Ribeirao Preto, SP, CEP: 14048-900, Brazil.
authors.forename: Rebeca Lopes
authors.initials: RL
authors.lastname: Figueira
authors.affiliation: Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Federico
authors.initials: F
authors.lastname: Scorletti
authors.affiliation: Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Peiró
authors.affiliation: Laboratory of Experimental Fetal Surgery, Division of Pediatric Surgery, Department of Surgery and Anatomy, Ribeirao Preto Medical School, University of Sao Paulo, Av. Bandeirantes, 3900, Ribeirao Preto, SP, CEP: 14048-900, Brazil. sbragia@fmrp.usp.br.
authors.forename: Lourenço
authors.initials: L
authors.lastname: Sbragia
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D021721:Balloon Occlusion / Q000379:methods*; D004195:Disease Models, Animal; D005260:Female; D065630:Hernias, Diaphragmatic, Congenital / Q000188:drug therapy* / Q000196:embryology; D011247:Pregnancy; D011270:Pregnancy, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D014132:Trachea; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D014212:Tretinoin
keywords: Congenital diaphragmatic hernia; Nitrofen; Rat model; Retinoic acid; Tracheal occlusion