| Dual endothelin receptor blockade with tezosentan markedly attenuates hypoxia induced pulmonary vasoconstriction in a porcine model. | |
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MedLine Citation:
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PMID: 21726419 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Aim: Our aim was to test the hypothesis that dual endothelin receptor blockade with tezosentan attenuates hypoxia induced pulmonary vasoconstriction. Methods: 14 anaesthetised, ventilated pigs, with a mean±SEM weight of 30,5±0,6 kg, were studied, in normoxia (FiO(2) ∼0,21) and with tezosentan (5mg·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 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 by 5,2±2,1 WU. Pulmonary capillary wedge pressure, mean aortic blood pressure, heart rate, cardiac output, stroke volume and blood-O(2) -consumption were unaltered (p=ns). Tezosentan infused during hypoxia, normalised pulmonary vascular resistance, decreased (p<0,05) maximally mean pulmonary artery pressure by 7,5±0,8 mmHg, systemic vascular resistance 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, pulmonary capillary wedge pressure, heart rate, cardiac output and blood-O(2) -consumption were unaltered (p=ns). Tezosentan infused before hypoxia additionally attenuated ∼70% of the initial mean pulmonary artery pressure increase and abolished the pulmonary vascular resistance 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 ∼62% and by normalising pulmonary vascular resistance. Pre-treatment with tezosentan before hypoxia, additionally attenuates the initial hypoxia induced mean pulmonary artery pressure rise by ∼70% and abolishes the pulmonary vascular resistance increase, during stable circulatory conditions, without affecting oxygenation. |
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Authors:
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Petter Hedelin; David Kylhammar; Göran Rådegran |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-7-4 |
Journal Detail:
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Title: Acta physiologica (Oxford, England) Volume: - ISSN: 1748-1716 ISO Abbreviation: - Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-7-5 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101262545 Medline TA: Acta Physiol (Oxf) Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Scandinavian Physiological Society. |
Affiliation:
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The Öresund Cardiovascular Research Collaboration The Clinic for Heart Failure and Valvular Disease Skåne University Hospital and Department of Cardiology, IKVL, Lund University Lund, Sweden The Copenhagen Muscle Research Centre Rigshospitalet and the Panum Institute, University of Copenhagen Copenhagen, Denmark Short title: Dual ET-Receptor Blockade Attenuates HPV. |
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