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Acute effect of a dual ETA–ETB receptor antagonist on pulmonary arterial vasculature in preterm lamb fetuses with surgically induced diaphragmatic hernia

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Abstract

Purpose

To study the effects of tezosentan, a dual ETA and ETB receptor antagonist on the cardiopulmonary profile in a fetal lamb model of CDH in utero.

Methods

A diaphragmatic hernia was surgically created at day 75 of gestation. During a 45 min of tezosentan perfusion (1 mg/kg), hemodynamic parameters (pulmonary and aortic pressures, left pulmonary and aortic flows, left auricle pressure, heart rate) were measured at day 135 of gestation. Age-matched fetal lambs served as control animals. Secondarily, parietal tension of vessels rings of pulmonary arteries was assessed in organ baths under increasing concentration of tezosentan.

Results

In CDH group, under perfusion of tezosentan, pulmonary artery pressure decreased from 45.8 ± 4.1 to 37.6 ± 5.9 mmHg (P < 0.05). Pulmonary artery flow and pulmonary vascular resistance remained constant. In control group, pulmonary artery flow increased from 153.9 ± 15.8 to 233.4 ± 26 ml/min (P < 0.05). Pulmonary artery pressure did not vary. Subsequently calculated pulmonary vascular resistance decreased. In organ bath, no significant relaxation was observed.

Conclusion

In this fetal lamb model of CDH, tezosentan decreased pulmonary artery pressure but did not modify pulmonary blood flow. Endothelin may play a role in the regulation of pulmonary vascular tone in utero.

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Authors and Affiliations

  1. Department of Pediatric Surgery, Hospital Timone Enfant, Marseille, France

    Eleuthère Stathopoulos, Géraldine Héry, Catherine de Magnée, Jean-Michel Guys & Pascal de Lagausie

  2. School of Medicine, Mediterranean University, Marseille, France

    Pierre-Henri Rolland

  3. Department of Anesthesiology, Intensive Care, Hospital Timone Enfant, Marseille, France

    Olivier Paut, Emmanuelle Couchot & Olivier Leprêtre

  4. Centre de référence des hernies diaphragmatiques, Marseille, France

    Emmanuelle Couchot & Pascal de Lagausie

Authors
  1. Eleuthère Stathopoulos
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  2. Pierre-Henri Rolland
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  3. Géraldine Héry
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  4. Catherine de Magnée
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  5. Olivier Paut
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  9. Pascal de Lagausie
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Correspondence to Eleuthère Stathopoulos.

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Stathopoulos, E., Rolland, PH., Héry, G. et al. Acute effect of a dual ETA–ETB receptor antagonist on pulmonary arterial vasculature in preterm lamb fetuses with surgically induced diaphragmatic hernia. Pediatr Surg Int 27, 295–301 (2011). https://doi.org/10.1007/s00383-010-2668-4

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