title: Effects of 5'-phosphodiesterase four-week long inhibition with sildenafil in patients with chronic heart failure: a double-blind, placebo-controlled clinical trial.
abstract: BACKGROUND
  The effects of chronic inhibition of 5'-phosphodiesterase with sildenafil on functional capacity, ventilatory efficiency, oxygen uptake, pulmonary hypertension, and endothelial function in chronic heart failure (CHF) are unknown.
  
  
  METHODS
  We conducted a randomized, double-blind, placebo-controlled trial to assess the acute (1 hour after 50 mg by mouth) and chronic (4 weeks after 50 mg 3 times per day by mouth) effects of sildenafil in outpatients with CHF. The outcomes were cardiopulmonary exercise test parameters (chronic effect), echocardiographic-derived pulmonary artery systolic pressure, and plethysmography-derived forearm blood flow (acute and chronic effects).
  
  
  RESULTS
  Nineteen patients with CHF (48 +/- 12 years) with an ejection fraction of 28% +/- 6% were studied. Patients who received sildenafil (n = 11) showed improved maximal oxygen uptake, ventilatory efficiency, and oxygen uptake kinetics. Sildenafil decreased pulmonary artery systolic pressure levels at 60 minutes and at 4 weeks compared with changes after placebo (P = .004 for group and time interaction). Improvement in ventilatory efficiency was positively associated with reductions in pulmonary artery systolic pressure. Patients allocated to placebo demonstrated a trend toward decreased forearm blood flow after reactive hyperemia, whereas this remained unchanged in patients allocated to sildenafil.
  
  
  CONCLUSIONS
  Sildenafil administration for 4 weeks in stable outpatients with CHF improves functional capacity, ventilatory efficiency, oxygen uptake kinetics, and pulmonary hypertension. These effects may be mediated in part by improvements in endothelial function.
authors.affiliation: Division of Cardiology, Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, RS.
authors.forename: Alice
authors.initials: A
authors.lastname: Behling
authors.forename: Luis E
authors.initials: LE
authors.lastname: Rohde
authors.forename: Fernanda C
authors.initials: FC
authors.lastname: Colombo
authors.forename: Livia A
authors.initials: LA
authors.lastname: Goldraich
authors.forename: Ricardo
authors.initials: R
authors.lastname: Stein
authors.forename: Nadine
authors.initials: N
authors.lastname: Clausell
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005080:Exercise Test; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D010879:Piperazines / Q000008:administration & dosage*; D010991:Plethysmography; D011336:Probability; D011687:Purines / Q000008:administration & dosage; D012016:Reference Values; D018570:Risk Assessment; D012720:Severity of Illness Index; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage*; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate; D010727:Phosphoric Diester Hydrolases