Influences of sildenafil on lung function and hemodynamics in patients with chronic heart failure

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

Research output: Contribution to journalArticle

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Abstract

Chronic heart failure (CHF) may be associated with a disordered nitric oxide (NO)-mediated regulation of the pulmonary vessel tone and permeability and of the gas transfer across the alveolar-capillary membrane. Whether enhancement of NO availability is beneficial with regard to these functions has not been explored. Phosphodiesterase 5 inhibitors, such as sildenafil, may provide a tool with which to test this possibility. In 10 patients with CHF and 10 normal subjects, before and at 60 minutes after sildenafil (50 mg) or placebo, we measured left ventricular ejection fraction, pulmonary hemodynamics, lung diffusion capacity for carbon monoxide and its alveolar-capillary membrane and blood capillary volume subcomponents, and flow-mediated brachial artery dilation (FMD) during reactive hyperemia to distal circulatory arrest (an indirect index of NO-mediated endothelial function). In patients with CHF, sildenafil caused no variations in ejection fraction, cardiac index, wedge pulmonary pressure, and blood capillary volume; it decreased pulmonary artery systolic (-21.6%) and diastolic (-31.8%) pressure and arteriolar resistance (-36.9%); and it increased lung diffusion capacity for carbon monoxide (+11.2%), diffusing capacity of the alveolar-capillary membrane (+10.6%), and FMD (from +8.3% to +13.4%). All changes were significant at P <.01. None of these effects was observed in healthy subjects. Placebo was ineffective in both patients and control subjects. This study provides the novel information that, in patients with CHF, phosphodiesterase 5 inhibition with sildenafil ameliorates the pulmonary hemodynamics and reduces the impedance of the alveolar-capillary interface, even if left ventricular filling pressure and function remain steady. The associated improvement in FMD at the periphery substantiates the possibility that an enhancement in NO release may underlie these effects.

Original languageEnglish
Pages (from-to)371-378
Number of pages8
JournalClinical Pharmacology and Therapeutics
Volume76
Issue number4
DOIs
Publication statusPublished - Oct 2004

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Heart Failure
Hemodynamics
Nitric Oxide
Lung
Lung Volume Measurements
Carbon Monoxide
Blood Volume
Membranes
Placebos
Type 5 Cyclic Nucleotide Phosphodiesterases
Phosphodiesterase 5 Inhibitors
Pulmonary Wedge Pressure
Brachial Artery
Ventricular Function
Hyperemia
Ventricular Pressure
Electric Impedance
Stroke Volume
Pulmonary Artery
Dilatation

ASJC Scopus subject areas

  • Pharmacology

Cite this

Influences of sildenafil on lung function and hemodynamics in patients with chronic heart failure. / Guazzi, Marco; Tumminello, Gabriele; Di Marco, Fabio; Guazzi, Maurizio D.

In: Clinical Pharmacology and Therapeutics, Vol. 76, No. 4, 10.2004, p. 371-378.

Research output: Contribution to journalArticle

Guazzi, Marco ; Tumminello, Gabriele ; Di Marco, Fabio ; Guazzi, Maurizio D. / Influences of sildenafil on lung function and hemodynamics in patients with chronic heart failure. In: Clinical Pharmacology and Therapeutics. 2004 ; Vol. 76, No. 4. pp. 371-378.
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