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


CONCLUSIONS
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.
Stathopoulos
Eleuthère
E
Department of Pediatric Surgery, Hospital Timone Enfant, Marseille, France. leftsta@hotmail.com
Rolland
Pierre-Henri
PH
Héry
Géraldine
G
de Magnée
Catherine
C
Paut
Olivier
O
Couchot
Emmanuelle
E
Leprêtre
Olivier
O
Guys
Jean-Michel
JM
de Lagausie
Pascal
P
D000818:Animals; D004195:Disease Models, Animal; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D005260:Female; D005333:Fetus / Q000503:physiopathology; D006439:Hemodynamics; D006548:Hernia, Diaphragmatic / Q000503:physiopathology; D065630:Hernias, Diaphragmatic, Congenital; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology*; D011247:Pregnancy; D011651:Pulmonary Artery / Q000503:physiopathology*; D011725:Pyridines / Q000494:pharmacology*; D012756:Sheep; D018709:Statistics, Nonparametric; D013777:Tetrazoles / Q000494:pharmacology*
D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D011725:Pyridines; D013777:Tetrazoles; C120582:tezosentan