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

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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.

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Acknowledgments

The authors thank Ms. Anne Riestenberg for her English assistance in the preparation of this manuscript.

Financial support

FAPESP—São Paulo Research Foundation—Research Grants #2008/50347-9, #2011/00794-1 and Scholarships #2008/52772-9, #2011/12587-0, # 2014/02519-6 and CNPq-Conselho Nacional de Desenvolvimento Científico e Tecnológico # 302433/2014-7.

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Authors and Affiliations

  1. Division of Neonatology and Pulmonary Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Augusto Frederico Schmidt

  2. 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

    Frances Lilian Lanhellas Gonçalves, Rebeca Lopes Figueira & Lourenço Sbragia

  3. Division of Pediatric General and Thoracic Surgery, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Federico Scorletti & Jose Luis Peiró

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  1. Augusto Frederico Schmidt
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Correspondence to Lourenço Sbragia.

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Schmidt, A.F., Gonçalves, F.L.L., Figueira, R.L. et al. Combined antenatal therapy with retinoic acid and tracheal occlusion in a rat model of congenital diaphragmatic hernia. Pediatr Surg Int 32, 591–598 (2016). https://doi.org/10.1007/s00383-016-3886-1

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