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Cyclooxygenase-2 inhibition and thromboxane A (2) receptor antagonism attenuate hypoxic pulmonary vasoconstriction in a porcine model.

Kylhammar, David LU and Rådegran, Göran LU (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:
author
organization
publishing date
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:84860523542
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
2012-06-02 16:17:25
date last changed
2017-01-01 03:38:39
@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 &lt; 0.001), pulmonary vascular resistance (PVR) by 2.7 ± 0.3 WU (P &lt; 0.05) and mean right atrial pressure by 2.3 ± 0.3 mmHg (P &lt; 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 &lt; 0.013), as well as PVR by 0.8 ± 0.2 WU (P &lt; 0.05), levelling off after 15 min. Daltroban transiently increased (P &lt; 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 &lt; 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},
  keyword      = {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},
  volume       = {205},
  year         = {2012},
}