Endothelium-mediated modulation of ergoreflex and improvement in exercise ventilation by acute sildenafil in heart failure patients

M. Guazzi, M. Casali, F. Berti, G. Rossoni, V. D'Gennaro Colonna, M. D. Guazzi

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Reflex neural oversignaling sensitive to muscle by-products (ergoreflex) causes exercise hyperventilation in heart failure (HF). We probed whether an improved endothelial function with sildenafil intake may prevent this effect. In 16 chronic heart failure patients and 16 normal subjects, before and after sildenafil intake (50 mg) or placebo, we measured ergoreflex, flow-mediated brachial artery dilation (FMD, an index of endothelial function), and, during maximal exercise, the slope of ventilation to carbon dioxide production (VE/VCO 2, an index of ventilatory efficiency), the ratio of changes in O 2 uptake (VO 2) versus work rate (WR) (ΔVO 2/ΔWR, an index of aerobic efficiency). After sildenafil intake, patients, unlike controls, showed a significant decrease in ergoreflex and VE/VCO 2 slope and an increase in FMD and ΔVO 2/ΔWR. Ergoreflex changes with sildenafil intake correlated with those in FMD and VE/VCO 2. Phosphodiesterase-5 inhibition, by improving endothelial activity and muscle perfusion, modulates signaling and improves ventilatory and aerobic efficiencies, potentially indicating a novel pathway in the HF therapeutic management.

Original languageEnglish
Pages (from-to)336-341
Number of pages6
JournalClinical Pharmacology and Therapeutics
Volume83
Issue number2
DOIs
Publication statusPublished - Feb 2008

Fingerprint

Endothelium
Ventilation
Heart Failure
Exercise
Efficiency
Type 5 Cyclic Nucleotide Phosphodiesterases
Muscles
Brachial Artery
Hyperventilation
Carbon Dioxide
Reflex
Dilatation
Perfusion
Placebos
Sildenafil Citrate
Therapeutics

ASJC Scopus subject areas

  • Pharmacology

Cite this

Endothelium-mediated modulation of ergoreflex and improvement in exercise ventilation by acute sildenafil in heart failure patients. / Guazzi, M.; Casali, M.; Berti, F.; Rossoni, G.; D'Gennaro Colonna, V.; Guazzi, M. D.

In: Clinical Pharmacology and Therapeutics, Vol. 83, No. 2, 02.2008, p. 336-341.

Research output: Contribution to journalArticle

Guazzi, M. ; Casali, M. ; Berti, F. ; Rossoni, G. ; D'Gennaro Colonna, V. ; Guazzi, M. D. / Endothelium-mediated modulation of ergoreflex and improvement in exercise ventilation by acute sildenafil in heart failure patients. In: Clinical Pharmacology and Therapeutics. 2008 ; Vol. 83, No. 2. pp. 336-341.
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