Combined antenatal therapy with retinoic acid and tracheal occlusion in a rat model of congenital diaphragmatic hernia

Augusto Frederico Schmidt, Frances Lilian Lanhellas Gonçalves, Rebeca Lopes Figueira, Federico Scorletti, Jose Luis Peiró, Lourenço Sbragia

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Aim: 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). Material and 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)591-598
Number of pages8
JournalPediatric Surgery International
Volume32
Issue number6
DOIs
StatePublished - Jun 1 2016
Externally publishedYes

Keywords

  • Congenital diaphragmatic hernia
  • Nitrofen
  • Rat model
  • Retinoic acid
  • Tracheal occlusion

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Surgery

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