Dual endothelin receptor blockade with tezosentan markedly attenuates hypoxia induced pulmonary vasoconstriction in a porcine model.
(2012) In Acta Physiologica 204(3). p.419-434- Abstract
- 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) â0,21) 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... (More)
- 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) â0,21) 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2059018
- author
- Hedelin, Petter ; Kylhammar, David LU and Rådegran, Göran LU
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- hypoxic pulmonary vasoconstriction, pulmonary hypertension, vascular tone, pulmonary
- in
- Acta Physiologica
- volume
- 204
- issue
- 3
- pages
- 419 - 434
- publisher
- Wiley-Blackwell
- external identifiers
-
- wos:000299775100014
- pmid:21726419
- scopus:84856557478
- pmid:21726419
- ISSN
- 1748-1708
- DOI
- 10.1111/j.1748-1716.2011.02339.x
- language
- English
- LU publication?
- yes
- id
- f367bee9-b978-4ee9-b292-8dabe4070f34 (old id 2059018)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/21726419?dopt=Abstract
- date added to LUP
- 2016-04-01 09:47:28
- date last changed
- 2022-02-17 03:16:22
@article{f367bee9-b978-4ee9-b292-8dabe4070f34,
abstract = {{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) â0,21) 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.}},
author = {{Hedelin, Petter and Kylhammar, David and Rådegran, Göran}},
issn = {{1748-1708}},
keywords = {{hypoxic pulmonary vasoconstriction; pulmonary hypertension; vascular tone; pulmonary}},
language = {{eng}},
number = {{3}},
pages = {{419--434}},
publisher = {{Wiley-Blackwell}},
series = {{Acta Physiologica}},
title = {{Dual endothelin receptor blockade with tezosentan markedly attenuates hypoxia induced pulmonary vasoconstriction in a porcine model.}},
url = {{http://dx.doi.org/10.1111/j.1748-1716.2011.02339.x}},
doi = {{10.1111/j.1748-1716.2011.02339.x}},
volume = {{204}},
year = {{2012}},
}