Hemodynamic and gas exchange effects of sildenafil in patients with chronic obstructive pulmonary disease and pulmonary hypertension

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 (V̇_A/Q̇) 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 -6mmHg (95% confidenc einterval [95%CI], -7 to -4) at rest and -11mmHg (95% CI, -14 to 28) during exercise. After sildenafil, Pa_O2 decreased -6mmHg (95% CI, -8 to -4) at rest because of increased perfusion in units with low V̇_A/Q̇ ratio, without differences between doses. No change in Pa_O2 (95% CI, -3 to 0.2 mm Hg) or V̇_A/Q̇ relationships occurred during exercise after sildenafil. Changes induced by sildenafil in Pa_O2 and V̇_A/Q̇ distributions at rest correlated with their respective values at baseline. Conclusions: In patients with COPD-associated PH, sildenafil improves pulmonary hemodynamics at rest and during exercise. This effect is accompanied by the inhibition of hypoxic vasoconstriction, which impairs arterial oxygenation at rest. The use of sildenafil in COPD should be done cautiously and under close monitoring of blood gases. Clinical trial registered with www.clinicaltrials.gov (NCT00491803).