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

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 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 &#xb1; 4.1 to 37.6 &#xb1; 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 &#xb1; 15.8 to 233.4 &#xb1; 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.