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 language | English |
|---|---|
| Pages (from-to) | 371-378 |
| Number of pages | 8 |
| Journal | Clinical Pharmacology and Therapeutics |
| Volume | 76 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Oct 2004 |
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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 journal › Article
}
TY - JOUR
T1 - Influences of sildenafil on lung function and hemodynamics in patients with chronic heart failure
AU - Guazzi, Marco
AU - Tumminello, Gabriele
AU - Di Marco, Fabio
AU - Guazzi, Maurizio D.
PY - 2004/10
Y1 - 2004/10
N2 - 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.
AB - 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.
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U2 - 10.1016/j.clpt.2004.06.003
DO - 10.1016/j.clpt.2004.06.003
M3 - Article
VL - 76
SP - 371
EP - 378
JO - Clinical Pharmacology and Therapeutics
JF - Clinical Pharmacology and Therapeutics
SN - 0009-9236
IS - 4
ER -