Cyclooxygenase‐2 inhibition and thromboxane A 2 receptor antagonism attenuate hypoxic pulmonary vasoconstriction in a porcine model

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.