Journal Article

Hemodynamic and Gas Exchange Effects of Sildenafil in Patients with Chronic Obstructive Pulmonary Disease and Pulmonary Hypertension

Gimeno, Elena, Blanco, Isabel, Gistau, Concepcion, Rodriguez-Roisin, Robert, Barbera, Joan Albert, Munoz, Phillip A, Roca, Josep, Pizarro, Sandra

2010

Overview

Abstract 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 ($\\mathrm{{\\dot{V}}}_{{\\mathrm{A}}}/\\mathrm{{\\dot{Q}}}$) 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, PaO2 decreased −6 mm Hg (95% CI, −8 to –4) at rest because of increased perfusion in units with low $\\mathrm{{\\dot{V}}}_{{\\mathrm{A}}}/\\mathrm{{\\dot{Q}}}$ ratio, without differences between doses. No change in PaO2 (95% CI, −3 to 0.2 mm Hg) or $\\mathrm{{\\dot{V}}}_{{\\mathrm{A}}}/\\mathrm{{\\dot{Q}}}$ relationships occurred during exercise after sildenafil. Changes induced by sildenafil in PaO2 and $\\mathrm{{\\dot{V}}}_{{\\mathrm{A}}}/\\mathrm{{\\dot{Q}}}$ 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).

• Publisher: Am Thoracic Soc,Oxford University Press,American Thoracic Society
• Subject: 3',5'-Cyclic-GMP Phosphodiesterases - antagonists & inhibitors / Aged / Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy / Biological and medical sciences / Chronic obstructive pulmonary disease / Dose-Response Relationship, Drug / Exercise - physiology / Exercise Test / Female / Follow-Up Studies / Gases / Hemodynamics / Hemodynamics - drug effects / Hemodynamics - physiology / Humans / Hypertension, Pulmonary - drug therapy / Hypertension, Pulmonary - etiology / Hypertension, Pulmonary - physiopathology / Hypoxia / Intensive care medicine / Male / Medical sciences / Middle Aged / Piperazines - administration & dosage / Piperazines - therapeutic use / Pneumology / Pulmonary Disease, Chronic Obstructive - complications / Pulmonary Disease, Chronic Obstructive - drug therapy / Pulmonary Disease, Chronic Obstructive - physiopathology / Pulmonary Gas Exchange - drug effects / Pulmonary Gas Exchange - physiology / Pulmonary hypertension / Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases / Pulmonary Wedge Pressure - drug effects / Pulmonary Wedge Pressure - physiology / Purines - administration & dosage / Purines - therapeutic use / Rest - physiology / Severity of Illness Index / Sildenafil Citrate / Sulfones - administration & dosage / Sulfones - therapeutic use / Treatment Outcome / Vasodilator Agents - administration & dosage / Vasodilator Agents - therapeutic use