Background-Pulmonary hypertension induced by chronic hypoxia is characterized by thickening of pulmonary artery walls, elevated pulmonary vascular resistance, and right-heart failure. Prostacyclin analogues reduce pulmonary pressures in this condition; raising the possibility that cycloxygenase-2 (COX-2) modulates the response of the pulmonary vasculature to hypoxia. Methods and Results-Sprague-Dawley rats in which pulmonary hypertension was induced by hypobaric hypoxia for 14 days were treated concurrently with the selective COX-2 inhibitor SC236 or vehicle. Mean pulmonary arterial pressure (mPAP) was elevated after hypoxia (28.1Ϯ3.2 versus 17.2Ϯ3.1 mm Hg; nϭ8, PϽ0.01), with thickening of small pulmonary arteries and increased COX-2 expression and prostacyclin formation. Selective inhibition of COX-2 aggravated the increase in mPAP (42.8Ϯ5.9 mm Hg; nϭ8, PϽ0.05), an effect that was attenuated by the thromboxane (TX) A 2 /prostaglandin endoperoxide receptor antagonist ifetroban. Urinary TXB 2 increased during hypoxia (5.9Ϯ0.9 versus 1.2Ϯ0.2 ng/mg creatinine; nϭ6, PϽ0.01) and was further increased by COX-2 inhibition (8.5Ϯ0.7 ng/mg creatinine; nϭ6, PϽ0.05). In contrast, urinary excretion of the prostacyclin metabolite 6-ketoprostaglandin F 1␣ decreased with COX-2 inhibition (8.6Ϯ3.0 versus 27.0Ϯ4.8 ng/mg creatinine; nϭ6, PϽ0.05). Platelet activation was enhanced after chronic hypoxia. COX-2 inhibition further reduced the PFA-100 closure time and enhanced platelet deposition in the smaller pulmonary arteries, effects that were attenuated by ifetroban. Mice with targeted disruption of the COX-2 gene exposed to chronic hypoxia had exacerbated right ventricular end-systolic pressure, whereas targeted disruption of COX-1 had no effect. Conclusions-COX-2 expression is increased and regulates platelet activity and intravascular thrombosis in hypoxiainduced pulmonary hypertension.

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SummaryWe assessed agreement between measurement of systemic oxygen uptake using the Fick-derived method, and a novel method described by Biro, based on the difference in oxygen concentrations of the delivered fresh gas and the gas circulating in the circle system. Twenty-nine patients undergoing elective cardiac surgery were studied during stable haemodynamic and ventilatory conditions. Systemic oxygen uptake was measured using the two methods in each patient before and after cardiopulmonary bypass. Limits of agreement were found to be wide ()162 to 311 ml.min )1 before bypass, and )257 to 401 ml.min )1 after bypass), indicating poor agreement between the methods. No significant difference was found between the pre-and post cardiopulmonary bypass values for each method. We conclude that the Biro method, although attractive in terms of its simplicity, is an unreliable measure of systemic oxygen uptake under these conditions.