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Cyclooxygenase‐2 inhibition and thromboxane A 2 receptor antagonism attenuate hypoxic pulmonary vasoconstriction in a porcine model
Author(s) -
Kylhammar D.,
Rådegran G.
Publication year - 2012
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/j.1748-1716.2012.02437.x
Subject(s) - hypoxic pulmonary vasoconstriction , pulmonary artery , medicine , hypoxia (environmental) , pulmonary hypertension , vascular resistance , vasoconstriction , cardiology , thromboxane receptor , thromboxane , anesthesia , mean arterial pressure , pulmonary wedge pressure , hemodynamics , blood pressure , thromboxane a2 , chemistry , receptor , heart rate , platelet , oxygen , organic chemistry
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. D altroban 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.