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Dual endothelin receptor blockade with tezosentan markedly attenuates hypoxia‐induced pulmonary vasoconstriction in a porcine model
Author(s) -
Hedelin P.,
Kylhammar D.,
Rådegran G.
Publication year - 2012
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/j.1748-1716.2011.02339.x
Subject(s) - hypoxic pulmonary vasoconstriction , medicine , vascular resistance , pulmonary wedge pressure , cardiac output , pulmonary artery , cardiology , anesthesia , hypoxia (environmental) , blood pressure , stroke volume , endothelin receptor , vasoconstriction , mean circulatory filling pressure , central venous pressure , heart rate , receptor , chemistry , organic chemistry , oxygen
Aim: Our aim was to test the hypothesis that dual endothelin receptor blockade with tezosentan attenuates hypoxia‐induced pulmonary vasoconstriction.Methods: Fourteen anaesthetized, ventilated pigs, with a mean ± SEM weight of 30.5 ± 0.6 kg, were studied, in normoxia (FiO 2 0.21) and with tezosentan (5 mg kg −1 ) infusion during ( n = 7) or before ( n = 7) hypoxia (FiO 2 0.10).Results: Compared to normoxia, hypoxia increased ( P < 0.05) pulmonary vascular resistance (PVR) by 3.4 ± 0.7 WU, mean pulmonary artery pressure by 13.7 ± 1.3 mmHg, mean right atrial pressure by 1.9 ± 0.4 mmHg and decreased ( P < 0.02) systemic vascular resistance (SVR) by 5.2 ± 2.1 WU. Pulmonary capillary wedge pressure (PCWP), mean aortic blood pressure, heart rate, cardiac output, stroke volume and blood‐O 2 ‐consumption were unaltered ( P = ns). Tezosentan infused during hypoxia, normalized PVR, decreased ( P < 0.05) maximally mean pulmonary artery pressure by 7.5 ± 0.8 mmHg, SVR by 5.8 ± 0.7 WU, mean aortic blood pressure by 10.8 ± 3.0 mmHg and increased ( P < 0.04) stroke volume by 8.5 ± 1.8 mL. Mean right atrial pressure, PCWP, heart rate, cardiac output and blood‐O 2 ‐consumption were unaltered ( P = ns). Tezosentan infused before hypoxia additionally attenuated approx. 70% of the initial mean pulmonary artery pressure increase and abolished the PVR increase, without additionally affecting the other parameters.Conclusion: Dual endothelin receptor blockade during hypoxia attenuates the ‘sustained’ acute pulmonary vasoconstrictor response by reducing the mean pulmonary artery pressure increase by approx. 62% and by normalizing PVR. Pre‐treatment with tezosentan before hypoxia, additionally attenuates the initial hypoxia‐induced mean pulmonary artery pressure rise by approx. 70% and abolishes the PVR increase, during stable circulatory conditions, without affecting oxygenation.