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Endothelin receptor blockade in canine oleic acid-induced lung injury
Ives Hubloue1, Dominique Biarent1, Sophia Abdel Kafi1
1Laboratory of Physiology, Faculty of Medicine, Erasme Campus of the Free University of Brussels, Erasme University Hospital, Brussels, Belgium.
Objective:
To investigate the effects of endogenous endothelins on pulmonary haemodynamics and gas exchange in oleic acid lung injury.
Design:
Prospective experimental study in dogs.
Setting:
Animal research laboratory in a university teaching hospital. SUBJECTS. Seventeen anaesthetised and ventilated mongrel dogs.
Interventions:
Nine pretreated dogs received an infusion of the endothelin A and B receptor antagonist bosentan (10 mg/kg) started before oleic acid. Eight treated dogs received bosentan started 90 min after oleic acid. Cardiac index (CI) was manipulated by inflating an inferior vena caval balloon or by opening a femoral arterio-venous bypass.
Measurements And Results:
Pulmonary vascular resistance was defined by measuring the gradient between mean pulmonary artery pressure (MPAP) and occluded PAP (PAOP) at five levels of CI. Intrapulmonary shunt was measured using the inert gas SF(6). Pretreatment with bosentan prevented the oleic acid-induced shift of (MPAP-PAOP)/CI plots to higher pressures, but did not affect the increase in intrapulmonary shunt. Treatment of established oleic acid lung injury with bosentan had no effect.
Conclusions:
Pretreatment, but not treatment, with bosentan, in the dose used, blunted the oleic acid-induced increase in pulmonary vascular resistance, suggesting that endothelins contribute to the increase in pulmonary vascular tone in the early stages of oleic acid lung injury.