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

• Published in: Clinical pharmacology and therapeutics 2004-10, Vol.76 (4), p.371-378
• Main Authors: Guazzi, Marco, Tumminello, Gabriele, Di Marco, Fabio, Guazzi, Maurizio D.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cardiovascular system; Heart Failure; Hemodynamics - drug effects; Humans; Lung - drug effects; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Phosphodiesterase Inhibitors - administration & dosage; Phosphodiesterase Inhibitors - pharmacology; Piperazines - administration & dosage; Piperazines - pharmacology; Purines; Respiratory Function Tests; Severity of Illness Index; Sildenafil Citrate; Sulfones; Vasodilator agents. Cerebral vasodilators
• ISSN: 0009-9236; 1532-6535
• DOI: 10.1016/j.clpt.2004.06.003

Background 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. Methods 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). Results 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. Conclusion 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. Clinical Pharmacology & Therapeutics (2004) 76, 371–378; doi:10.1016/j.clpt.2004.06.003