Cyclooxygenase-2 inhibition and thromboxane A (2) receptor antagonism attenuate hypoxic pulmonary vasoconstriction in a porcine model.
(2012) In Acta Physiologica 205(4). p.507-519- Abstract
- AIM:
Hypoxic pulmonary vasoconstriction (HPV) causes pulmonary hypertension that may lead to right heart failure. We hypothesized that the COX-2 inhibitor nimesulide and the thromboxane A (2) receptor antagonist daltroban would attenuate HPV.
METHODS:
Haemodynamic measurements and blood sampling were performed in 18 anaesthetized, mechanically ventilated pigs, with mean ± SEM weights of 31.3 ± 0.6 kg, in normoxia (F (i) O (2) ~0.21) and hypoxia (F (i) O (2) ~0.10), before and 5, 15 and 45 min after initiation of right atrial infusion of nimesulide (n = 6) or daltroban (n = 6), respectively, and in six control pigs.
RESULTS:
Compared with normoxia, hypoxia (n = 18)... (More) - AIM:
Hypoxic pulmonary vasoconstriction (HPV) causes pulmonary hypertension that may lead to right heart failure. We hypothesized that the COX-2 inhibitor nimesulide and the thromboxane A (2) receptor antagonist daltroban would attenuate HPV.
METHODS:
Haemodynamic measurements and blood sampling were performed in 18 anaesthetized, mechanically ventilated pigs, with mean ± SEM weights of 31.3 ± 0.6 kg, in normoxia (F (i) O (2) ~0.21) and hypoxia (F (i) O (2) ~0.10), before and 5, 15 and 45 min after initiation of right atrial infusion of nimesulide (n = 6) or daltroban (n = 6), respectively, and in six control pigs.
RESULTS:
Compared with normoxia, hypoxia (n = 18) increased mean pulmonary artery pressure by 15.8 ± 0.8 mmHg (P < 0.001), pulmonary vascular resistance (PVR) by 2.7 ± 0.3 WU (P < 0.05) and mean right atrial pressure by 2.3 ± 0.3 mmHg (P < 0.001). In the control pigs, mean pulmonary artery pressure, PVR and mean right atrial pressure remained stable (P = ns) throughout 45 min hypoxia, compared with hypoxia baseline. Nimesulide decreased mean pulmonary artery pressure by 3.7 ± 1.3 mmHg after 45 min (P < 0.013), as well as PVR by 0.8 ± 0.2 WU (P < 0.05), levelling off after 15 min. Daltroban transiently increased (P < 0.001) mean pulmonary artery pressure and mean right atrial pressure by 7.2 ± 1.2 and 2.7 ± 0.4 mmHg, respectively, but they returned to hypoxia baseline (P = ns) within 5 min. Daltroban then decreased mean pulmonary artery pressure to after 45 min be 4.2 ± 1.6 mmHg lower (P < 0.005) than at hypoxia baseline.
CONCLUSION:
COX-2 inhibition and thromboxane A(2) receptor antagonism attenuate HPV by decreasing mean pulmonary artery pressure by approximately 10-11%, as measured 45 min after initiation of nimesulide or daltroban infusion respectively. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2609194
- author
- Kylhammar, David LU and Rådegran, Göran LU
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- hypoxia, eicosanoids, pulmonary hypertension
- in
- Acta Physiologica
- volume
- 205
- issue
- 4
- pages
- 507 - 519
- publisher
- Wiley-Blackwell
- external identifiers
-
- wos:000305824100006
- pmid:22554045
- scopus:85027954859
- ISSN
- 1748-1708
- DOI
- 10.1111/j.1748-1716.2012.02437.x
- language
- English
- LU publication?
- yes
- id
- f600d684-c627-48d5-8432-66f81fc4964a (old id 2609194)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/22554045?dopt=Abstract
- date added to LUP
- 2016-04-01 10:29:40
- date last changed
- 2022-01-25 23:48:37
@article{f600d684-c627-48d5-8432-66f81fc4964a,
abstract = {{AIM: <br/><br>
Hypoxic pulmonary vasoconstriction (HPV) causes pulmonary hypertension that may lead to right heart failure. We hypothesized that the COX-2 inhibitor nimesulide and the thromboxane A (2) receptor antagonist daltroban would attenuate HPV. <br/><br>
<br/><br>
METHODS: <br/><br>
Haemodynamic measurements and blood sampling were performed in 18 anaesthetized, mechanically ventilated pigs, with mean ± SEM weights of 31.3 ± 0.6 kg, in normoxia (F (i) O (2) ~0.21) and hypoxia (F (i) O (2) ~0.10), before and 5, 15 and 45 min after initiation of right atrial infusion of nimesulide (n = 6) or daltroban (n = 6), respectively, and in six control pigs. <br/><br>
<br/><br>
RESULTS: <br/><br>
Compared with normoxia, hypoxia (n = 18) increased mean pulmonary artery pressure by 15.8 ± 0.8 mmHg (P < 0.001), pulmonary vascular resistance (PVR) by 2.7 ± 0.3 WU (P < 0.05) and mean right atrial pressure by 2.3 ± 0.3 mmHg (P < 0.001). In the control pigs, mean pulmonary artery pressure, PVR and mean right atrial pressure remained stable (P = ns) throughout 45 min hypoxia, compared with hypoxia baseline. Nimesulide decreased mean pulmonary artery pressure by 3.7 ± 1.3 mmHg after 45 min (P < 0.013), as well as PVR by 0.8 ± 0.2 WU (P < 0.05), levelling off after 15 min. Daltroban transiently increased (P < 0.001) mean pulmonary artery pressure and mean right atrial pressure by 7.2 ± 1.2 and 2.7 ± 0.4 mmHg, respectively, but they returned to hypoxia baseline (P = ns) within 5 min. Daltroban then decreased mean pulmonary artery pressure to after 45 min be 4.2 ± 1.6 mmHg lower (P < 0.005) than at hypoxia baseline. <br/><br>
<br/><br>
CONCLUSION: <br/><br>
COX-2 inhibition and thromboxane A(2) receptor antagonism attenuate HPV by decreasing mean pulmonary artery pressure by approximately 10-11%, as measured 45 min after initiation of nimesulide or daltroban infusion respectively.}},
author = {{Kylhammar, David and Rådegran, Göran}},
issn = {{1748-1708}},
keywords = {{hypoxia; eicosanoids; pulmonary hypertension}},
language = {{eng}},
number = {{4}},
pages = {{507--519}},
publisher = {{Wiley-Blackwell}},
series = {{Acta Physiologica}},
title = {{Cyclooxygenase-2 inhibition and thromboxane A (2) receptor antagonism attenuate hypoxic pulmonary vasoconstriction in a porcine model.}},
url = {{http://dx.doi.org/10.1111/j.1748-1716.2012.02437.x}},
doi = {{10.1111/j.1748-1716.2012.02437.x}},
volume = {{205}},
year = {{2012}},
}