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Rationale: Sildenafil, a phosphodiesterase-5 inhibitor, could be useful for treating pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD). However, vasodilators may inhibit hypoxic pulmonary vasoconstriction and impair gas exchange in this condition.

Objectives: To assess the acute hemodynamic and gas exchange effects of sildenafil in patients with COPD-associated PH.

Methods: We conducted a randomized, dose comparison trial in 20 patients with COPD-associated PH. Eleven patients were assigned to 20 mg, and 9 patients to 40 mg, of sildenafil. Pulmonary hemodynamics and gas exchange, including ventilation-perfusion ([latin capital V with dot above]A/[Latin capital letter Q with dot above]) relationships, were assessed at rest and during constant-work rate exercise, before and 1 hour after sildenafil administration.

Measurements and Main Results: Both sildenafil doses reduced the mean pulmonary arterial pressure (PAP) at rest and during exercise, without differences between them. Overall, PAP decreased -6 mm Hg (95% confidence interval [95% CI], -7 to -4) at rest and -11 mm Hg (95% CI, -14 to -8) during exercise. After sildenafil, Symbol decreased -6 mm Hg (95% CI, -8 to -4) at rest because of increased perfusion in units with low [latin capital V with dot above]A/[Latin capital letter Q with dot above] ratio, without differences between doses. No change in Symbol (95% CI, -3 to 0.2 mm Hg) or [latin capital V with dot above]A/[Latin capital letter Q with dot above] relationships occurred during exercise after sildenafil. Changes induced by sildenafil in Symbol and [latin capital V with dot above]A/[Latin capital letter Q with dot above] distributions at rest correlated with their respective values at baseline.

(C) 2010 American Thoracic Society