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Dual endothelin receptor blockade with tezosentan markedly attenuates hypoxia induced pulmonary vasoconstriction in a porcine model.

Hedelin, Petter; Kylhammar, David LU and Rådegran, Göran LU (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)
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author
organization
publishing date
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
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
2011-08-01 17:38:46
date last changed
2017-04-02 03:00:06
@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&lt;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&lt;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&lt;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&lt;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},
  keyword      = {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},
  volume       = {204},
  year         = {2012},
}