The effects of phosphodiesterase-5 inhibition with sildenafil on pulmonary hemodynamics and diffusion capacity, exercise ventilatory efficiency, and oxygen uptake kinetics in chronic heart failure

OBJECTIVES We sought to investigate the effects of sildenafil, a phosphodiesterase-5 (PDE5) inhibitor, on lung function and exercise performance in chronic heart failure (CHF). BACKGROUND In CHF, nitric oxide-mediated regulation of lung vascular tone and alveolar-capillary membrane conductance is impaired and contributes to exercise intolerance. The potential for benefits due to increased nitric-oxide availability is unexplored. METHODS In 16 patients with CHF and 8 normal subjects, we measured-before and 60 min after sildenafil (50 mg) or placebo-ejection fraction, pulmonary hemodynamics, carbon monoxide diffusion capacity (DLco), with its membrane (D-M) and capillary blood volume (V-c) subcomponents, endothelial function (brachial reactive hyperemia) at rest, peak oxygen uptake (VO2), increments in VO2 versus work rate (DeltaVO(2)/DeltaWR), changes in ventilation versus CO2 production (VE/VCO2) slope, and recovery VO2 time constant (tau) on exertion. RESULTS In CHF, sildenafil did not affect cardiac index, wedge pulmonary pressure, or ejection fraction; it significantly (p < 0.01) decreased pulmonary mean artery pressure (-20.4%) and arteriolar resistance (-45.1%), VE/VCO2 slope (-9.0%) and recovery tau (-25.8%), and increased (p < 0.01) DLco (+11.1%), D-M (+9.9%) peak VO2 (+19.7%), DeltaVO(2)/DeltaWR (+11.0%), and brachial reactive hyperemia (+33.3%). No variations occurred in normal subjects and after placebo. Changes in DLco were related to those in VE/VCO2 slope (r = -0.71; p = 0.002), and changes in brachial hyperemia correlated with those in DeltaVO(2)/DeltaWR (r = 0.80; p = 0.0002). CONCLUSIONS This study shows that in CHF PDE5 inhibition modulates pulmonary pressure and vascular tone, and improves DLco, exercise peak VO2, aerobic (DeltaVO(2)/DeltaWR) and ventilatory (VE/VCO2 slope) efficiencies, and oxygen debt (recovery tau). Endothelial mechanisms may underlie these effects. (C) 2004 by the American College of Cardiology Foundation.