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Pediatric Surgery International

, Volume 29, Issue 5, pp 489–494 | Cite as

Increased contractility and impaired relaxation of the left pulmonary artery in a rabbit model of congenital diaphragmatic hernia

  • Augusto Frederico Schmidt
  • Julio Alejandro Rojas-Moscoso
  • Frances Lilian Lanhellas Gonçalves
  • Rodrigo Melo Gallindo
  • Fabíola Zakia Mónica
  • Edson Antunes
  • Rebeca Lopes Figueira
  • Lourenço Sbragia
Original Article

Abstract

Purpose

Congenital diaphragmatic hernia (CDH) is associated with pulmonary hypertension which is often difficult to manage and a significant cause of morbidity and mortality. Our aim was to study the pulmonary artery reactivity in an animal model of CDH.

Methods

To investigate the reactivity of the aorta and left pulmonary artery in a rabbit model of CDH, we studied the in vitro responses to the α1-adrenoceptor agonist phenylephrine (PE) and to both the muscarinic receptor agonist (ACh) and the nitric oxide (NO) donor sodium nitroprusside (SNP). Rabbits underwent surgery at 25 days of gestation. CDH was created in one fetus per horn (n = 8). Remaining fetuses were considered controls (n = 18). At term (30 days), the lung, left pulmonary artery, and aorta were dissected. In a separate group, endothelium was mechanically removed.

Results

There were no differences in the contractile and relaxing responses of aorta in all groups. In left pulmonary artery, PE-induced contractions were significantly greater (p < 0.05) in CDH when compared with control group. The increased responsiveness to PE in CDH group was similar to that found in pulmonary artery without endothelium. The ACh-induced pulmonary artery relaxation was markedly reduced in CDH when compared with control group (p < 0.05), whereas no differences were found for SNP.

Conclusion

Our results show increased contractility and impairment in endothelium-dependent relaxation of pulmonary artery in CDH, mimicking an endothelial dysfunction, with preserved response to endothelium-independent mechanism.

Keywords

Congenital diaphragmatic hernia Vascular reactivity Left pulmonary artery Endothelial dysfunction Rabbit 

Notes

Acknowledgments

We are grateful to Dr. Haroldo Alfredo Flores Toque for his help during the pharmacological procedures and to The National Council for Scientific and Technological Development (CNPq)—Brazil for financial support (Grant # 471496/2011-1).

References

  1. 1.
    Harrison MR, Adzick NS, Estes JM, Howell LJ (1994) A prospective study of the outcome for fetuses with diaphragmatic hernia. JAMA 271:382–384PubMedCrossRefGoogle Scholar
  2. 2.
    Tonks A, Wyldes M, Somerset DA et al (2004) Congenital malformations of the diaphragm: findings of the West Midlands Congenital Anomaly Register 1995 to 2000. Prenatal Diagn 24:596–604CrossRefGoogle Scholar
  3. 3.
    Kitagawa M, Hislop A, Boyde E, Reid L (1971) Lung hypoplasia in congenital diaphragmatic hernia. A quantitative study of airway artery and alveolar development. Br J Surg 58:342–346PubMedCrossRefGoogle Scholar
  4. 4.
    Geggel RL, Murphy JD, Langleben D, Crone RK, Vacanti JP, Reid LM (1985) Congenital diaphragmatic hernia: arterial structural changes and persistent pulmonary hypertension after surgical repair. J Pediatr 107:457–464PubMedCrossRefGoogle Scholar
  5. 5.
    O’Toole SJ, Irish MS, Holm BA, Glick PL (1996) Pulmonary vascular abnormalities in congenital diaphragmatic hernia. Clin Perinatol 23(4):781–794PubMedGoogle Scholar
  6. 6.
    De Mello DE, Sawyer D, Galvin N, Reid LM (1997) Early fetal development of lung vasculature. Am J Respir Cell Mol Biol 16(5):568–581CrossRefGoogle Scholar
  7. 7.
    Shinkai T, Shima H, Solari V, Puri P (2005) Expression of vasoactive mediators during mechanical ventilation in nitrofen-induced diaphragmatic hernia in rats. Pediatr Surg Int 21:143–147PubMedCrossRefGoogle Scholar
  8. 8.
    Cilley RE, Zgleszewski SE, Krummel TM, Chinoy MR (1997) Nitrofen dose-dependent gestational day-specific murine lung hypoplasia and left-sided congenital diaphragmatic hernia. Am J Physiol Lung Cell Mol Physiol 272:L362–L371Google Scholar
  9. 9.
    Ting A, Glick PL, Wilcox DT, Holm BA, Gil J, DiMaio M (1998) Alveolar vascularization of the lung in a lamb model of congenital diaphragmatic hernia. Am J Rep Crit Care Med 157(1):31–34CrossRefGoogle Scholar
  10. 10.
    Roubliova X, Verbeken E, Wu J, Yamamoto H, Lerut T, Tibboel D, Deprest J (2004) Pulmonary vascular morphology in a fetal rabbit model of congenital diaphragmatic hernia. J Pediatr Surg 39(7):1066–1072PubMedCrossRefGoogle Scholar
  11. 11.
    O’Toole SJ, Karamanoukian FC, Mourin FC, Holm BA, Egan EA, Azizkhan RG, Glick PL (1996) Surfactant decreases pulmonary vascular resistance and increases pulmonary blood flow in the fetal lamb model of congenital diaphragmatic hernia. J Pediatr Surg 31:507–511PubMedCrossRefGoogle Scholar
  12. 12.
    Sylvester KG, Rasanen J, Kitano Y, Flake AW, Cromblehome TM, Adzick NS (1998) Tracheal occlusion reverses the high impedance to blood flow in the fetal pulmonary circulation and normalized its physiological response to oxygen at full term. J Pediatr Surg 33:1071–1075PubMedCrossRefGoogle Scholar
  13. 13.
    Luong C, Rey-Perra J, Vadivel A, Gilmour G, Sauve Y, Koonen D, Walker D, Todd KG, Greesens P, Kassiri Z, Nadeem K, Morgan B, Eaton F, Dyck JR, Archer SL, Thebaud B (2011) Antenatal sildenafil treatment attenuates pulmonary hypertension in experimental congenital diaphragmatic hernia. Circulation 123:2120–2131PubMedCrossRefGoogle Scholar
  14. 14.
    Tulloh RM, Hislop AA, Boels PJ, Deutsch J, Haworth SG (1997) Chronic hypoxia inhibits postnatal maturation of porcine intrapulmonary artery relaxation. Am J Physiol 272:H2436–H2445PubMedGoogle Scholar
  15. 15.
    Kelly DA, Hislop AA, Hall SM, Haworth SG (2005) Relationship between structural remodeling and reactivity in pulmonary resistance arteries from hypertensive piglets. Pediatr Res 58:525–530PubMedCrossRefGoogle Scholar
  16. 16.
    Fauza DO, Tannuri U, Ayoub AA, Capelozzi VL, Saldiva PH, Maksoud JG (1994) Surgically produced congenital diaphragmatic hernia in fetal rabbits. J Pediatr Surg 29(7):882–886PubMedCrossRefGoogle Scholar
  17. 17.
    Zussman ME, Bagby M, Benson DW, Gupta R, Hirsch R (2012) Pumonary vascular resistance in repaired congenital diaphragmatic hernia vs. age-matched controls. Pediatr Res 71(6):697–700PubMedCrossRefGoogle Scholar
  18. 18.
    Peralta CF, Sbragia L, Bennini JR, Cavalli RC, Rousselet MS, Barini R (2011) Tracheal occlusion for fetuses with severe isolated left-sided diaphragmatic hernia: a randomized controlled experimental study. Rev Bras Ginecol 33(12):381–387Google Scholar
  19. 19.
    Jani J, Nicolaides KH, Gratacos E, Valencia CM, Done E, Martinez JM, Gucciardo L, Cruz R, Deprest JA (2009) Severe diaphragmatic hernia treated by fetal endoscopic tracheal occlusion. Ultrasound Obstet Gynecol 34(3):304–310PubMedCrossRefGoogle Scholar
  20. 20.
    Roubliova XI, Lewi PJ, Verbeken EK, Vaast P, Jani JC, Tibboel D, Deprest JA (2009) The effect of maternal betamethasone and fetal tracheal occlusion on pulmonary vascular morphometry in fetal rabbits with surgically induced diaphragmatic hernia: a placebo controlled morophologic study. Prenat Diagn 29(7):674–681PubMedCrossRefGoogle Scholar
  21. 21.
    Schmidt AF, Goncalves FL, Nassr AC, Pereira LA, Farmer D, Sbragia L (2010) Antenatal steroid and tracheal occlusion restore vascular endothelial growth factor receptors in congenital diaphragmatic hernia rat model. Am J Obstet Gynecol 23(2):184.e13–184.e20CrossRefGoogle Scholar
  22. 22.
    Schmidt AF, Goncalves FL, Regis AC, Gallindo RM, Sbragia L (2012) Prenatal retinoic acid improves lung vascularization and VEGF expression in CDH rat model. Am J Obstet Gynecol 207(1):76.e25–76.e32CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Augusto Frederico Schmidt
    • 1
  • Julio Alejandro Rojas-Moscoso
    • 2
  • Frances Lilian Lanhellas Gonçalves
    • 3
  • Rodrigo Melo Gallindo
    • 3
  • Fabíola Zakia Mónica
    • 2
  • Edson Antunes
    • 2
  • Rebeca Lopes Figueira
    • 3
  • Lourenço Sbragia
    • 3
  1. 1.Cincinnati Children’s Hospital Medical CenterCincinnatiUSA
  2. 2.Department of Pharmacology, School of Medical SciencesState University of CampinasCampinasBrazil
  3. 3.Laboratory of Experimental Fetal Surgery “Michael R Harrison”, Department of Surgery and Anatomy, School of Medicine of Ribeirao PretoUniversity of Sao Paulo, USPRibeirao PretoBrazil

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