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- Title
Cyclooxygenase-2 inhibition and thromboxane A<sub>2</sub> receptor antagonism attenuate hypoxic pulmonary vasoconstriction in a porcine model.
- Authors
Kylhammar, D.; Rådegran, G.
- 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 A2 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 ( Fi O2~0.21) and hypoxia ( Fi O2~0.10), 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 A2 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.
- Subjects
CYCLOOXYGENASE 2 inhibitors; THROMBOXANES; VASOCONSTRICTION; HEART failure; NIMESULIDE; LABORATORY swine
- Publication
Acta Physiologica, 2012, Vol 205, Issue 4, p507
- ISSN
1748-1708
- Publication type
Article
- DOI
10.1111/j.1748-1716.2012.02437.x