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 Original Research Article

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 (DM) and capillary blood volume (Vc) subcomponents, endothelial function (brachial reactive hyperemia) at rest, peak oxygen uptake (VO2), increments in VO2 versus work rate (ΔVO2/ΔWR), 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%), DM (+9.9%) peak VO2 (+19.7%), ΔVO2/ΔWR (+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 ΔVO2/ΔWR (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 (ΔVO2/ΔWR) and ventilatory (VE/VCO2 slope) efficiencies, and oxygen debt (recovery tau). Endothelial mechanisms may underlie these effects.