Ives Hubloue1, Dominique Biarent1, Sophia Abdel Kafi1, Gilbert Bejjani1, Christian Mélot1, Robert Naeije1, Marc Leeman2,3. 1. Laboratory of Physiology, Faculty of Medicine, Erasme Campus of the Free University of Brussels, Erasme University Hospital, Brussels, Belgium. 2. Department of Intensive Care, Erasme University Hospital, 808 Lennik Road, 1070, Brussels, Belgium. marc.leeman@ulb.ac.be. 3. Laboratory of Physiology, Faculty of Medicine, Erasme Campus of the Free University of Brussels, Erasme University Hospital, Brussels, Belgium. marc.leeman@ulb.ac.be.
Abstract
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.
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.
Authors: M Clozel; V Breu; G A Gray; B Kalina; B M Löffler; K Burri; J M Cassal; G Hirth; M Müller; W Neidhart Journal: J Pharmacol Exp Ther Date: 1994-07 Impact factor: 4.030
Authors: Edward Abraham; Peter Andrews; Massimo Antonelli; Laurent Brochard; Christian Brun-Buisson; Geoffrey Dobb; Jean-Yves Fagon; Johan Groeneveld; Jordi Mancebo; Philipp Metnitz; Stefano Nava; Michael Pinsky; Peter Radermacher; Marco Ranieri; Christian Richard; Robert Tasker; Benoit Vallet Journal: Intensive Care Med Date: 2004-06-26 Impact factor: 17.440
Authors: Timothy E Morey; Jerome H Modell; Dushyant Shekhawat; Todd Grand; Dinesh O Shah; Nikolaus Gravenstein; Susan P McGorray; Donn M Dennis Journal: Anesthesiology Date: 2006-06 Impact factor: 7.892
Authors: Laura C Price; Danny F McAuley; Philip S Marino; Simon J Finney; Mark J Griffiths; Stephen John Wort Journal: Am J Physiol Lung Cell Mol Physiol Date: 2012-01-13 Impact factor: 5.464
Authors: Alejandro P Comellas; Arturo Briva; Laura A Dada; Maria L Butti; Humberto E Trejo; Cecilia Yshii; Zaher S Azzam; Juan Litvan; Jiwang Chen; Emilia Lecuona; Liuska M Pesce; Masashi Yanagisawa; Jacob I Sznajder Journal: Am J Respir Crit Care Med Date: 2008-10-23 Impact factor: 21.405
Authors: Dmitry N Grigoryev; Shwu-Fan Ma; Brett A Simon; Rafael A Irizarry; Shui Q Ye; Joe G N Garcia Journal: BMC Genomics Date: 2005-05-04 Impact factor: 3.969