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

Marco Guazzi, Gabriele Tumminello, Fabio Di Marco, Cesare Fiorentini, Maurizio D. Guazzi

Research output: Contribution to journalArticle

Abstract

We sought to investigate the effects of sildenafil, a phosphodiesterase-5 (PDE 5) inhibitor, on lung function and exercise performance in chronic heart failure (CHF). 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. 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 (VO 2), increments in VO 2 versus work rate (ΔVO 2/ΔWR), changes in ventilation versus CO 2 production (VE/VCO 2) slope, and recovery VO 2 time constant (tau) on exertion. 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/VCO 2 slope (-9.0%) and recovery tau (-25.8%), and increased (p <0.01) DLco (+11.1%), D M (+9.9%) peak VO 2 (+19.7%), ΔVO 2/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/VCO 2 slope (r = -0.71; p = 0.002), and changes in brachial hyperemia correlated with those in ΔVO 2/ΔWR (r = 0.80; p = 0.0002). This study shows that in CHF PDE 5 inhibition modulates pulmonary pressure and vascular tone, and improves DLco, exercise peak VO 2, aerobic (ΔVO 2/ΔWR) and ventilatory (VE/VCO 2 slope) efficiencies, and oxygen debt (recovery tau). Endothelial mechanisms may underlie these effects.

Original languageEnglish
Pages (from-to)2339-2348
Number of pages10
JournalJournal of the American College of Cardiology
Volume44
Issue number12
DOIs
Publication statusPublished - Dec 21 2004

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Type 5 Cyclic Nucleotide Phosphodiesterases
Carbon Monoxide
Heart Failure
Hemodynamics
Ventilation
Exercise
Oxygen
Hyperemia
Lung
Arm
Blood Vessels
Nitric Oxide
Placebos
Phosphodiesterase 5 Inhibitors
Pressure
Pulmonary Wedge Pressure
Membranes
Blood Volume
Pulmonary Artery
Sildenafil Citrate

ASJC Scopus subject areas

  • Nursing(all)

Cite this

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title = "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",
abstract = "We sought to investigate the effects of sildenafil, a phosphodiesterase-5 (PDE 5) inhibitor, on lung function and exercise performance in chronic heart failure (CHF). 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. 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 (VO 2), increments in VO 2 versus work rate (ΔVO 2/ΔWR), changes in ventilation versus CO 2 production (VE/VCO 2) slope, and recovery VO 2 time constant (tau) on exertion. 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/VCO 2 slope (-9.0{\%}) and recovery tau (-25.8{\%}), and increased (p <0.01) DLco (+11.1{\%}), D M (+9.9{\%}) peak VO 2 (+19.7{\%}), ΔVO 2/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/VCO 2 slope (r = -0.71; p = 0.002), and changes in brachial hyperemia correlated with those in ΔVO 2/ΔWR (r = 0.80; p = 0.0002). This study shows that in CHF PDE 5 inhibition modulates pulmonary pressure and vascular tone, and improves DLco, exercise peak VO 2, aerobic (ΔVO 2/ΔWR) and ventilatory (VE/VCO 2 slope) efficiencies, and oxygen debt (recovery tau). Endothelial mechanisms may underlie these effects.",
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T1 - 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

AU - Guazzi, Marco

AU - Tumminello, Gabriele

AU - Di Marco, Fabio

AU - Fiorentini, Cesare

AU - Guazzi, Maurizio D.

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N2 - We sought to investigate the effects of sildenafil, a phosphodiesterase-5 (PDE 5) inhibitor, on lung function and exercise performance in chronic heart failure (CHF). 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. 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 (VO 2), increments in VO 2 versus work rate (ΔVO 2/ΔWR), changes in ventilation versus CO 2 production (VE/VCO 2) slope, and recovery VO 2 time constant (tau) on exertion. 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/VCO 2 slope (-9.0%) and recovery tau (-25.8%), and increased (p <0.01) DLco (+11.1%), D M (+9.9%) peak VO 2 (+19.7%), ΔVO 2/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/VCO 2 slope (r = -0.71; p = 0.002), and changes in brachial hyperemia correlated with those in ΔVO 2/ΔWR (r = 0.80; p = 0.0002). This study shows that in CHF PDE 5 inhibition modulates pulmonary pressure and vascular tone, and improves DLco, exercise peak VO 2, aerobic (ΔVO 2/ΔWR) and ventilatory (VE/VCO 2 slope) efficiencies, and oxygen debt (recovery tau). Endothelial mechanisms may underlie these effects.

AB - We sought to investigate the effects of sildenafil, a phosphodiesterase-5 (PDE 5) inhibitor, on lung function and exercise performance in chronic heart failure (CHF). 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. 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 (VO 2), increments in VO 2 versus work rate (ΔVO 2/ΔWR), changes in ventilation versus CO 2 production (VE/VCO 2) slope, and recovery VO 2 time constant (tau) on exertion. 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/VCO 2 slope (-9.0%) and recovery tau (-25.8%), and increased (p <0.01) DLco (+11.1%), D M (+9.9%) peak VO 2 (+19.7%), ΔVO 2/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/VCO 2 slope (r = -0.71; p = 0.002), and changes in brachial hyperemia correlated with those in ΔVO 2/ΔWR (r = 0.80; p = 0.0002). This study shows that in CHF PDE 5 inhibition modulates pulmonary pressure and vascular tone, and improves DLco, exercise peak VO 2, aerobic (ΔVO 2/ΔWR) and ventilatory (VE/VCO 2 slope) efficiencies, and oxygen debt (recovery tau). Endothelial mechanisms may underlie these effects.

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