title: Haemodynamic effects of rolofylline in the treatment of patients with heart failure and impaired renal function.
abstract: The direct effects of adenosine A1 receptor antagonists on haemodynamic parameters in patients with acute heart failure (HF) remain largely unknown.
  
  
  
  We evaluated the haemodynamic effects of the AA(1)RA rolofylline in 59 HF patients with concomitant renal impairment (estimated creatinine clearance 20-80 mL/min). Placebo or rolofylline 30 mg was administered as a 4 h infusion followed by intravenous (i.v.) loop diuretic administration. Haemodynamic measurements were carried out hourly up to 8 h post-dosing by pulmonary artery catheterization. Urine output, fractional excretion of sodium, potassium, urea, and uric acid, and blood urea nitrogen (BUN) and creatinine levels were also measured. In both groups, the changes from baseline in all haemodynamic indices except mean pulmonary artery pressure (PAP) were not clinically significant. Mean [95% confidence interval (CI)] PAP showed a placebo-adjusted decrease with rolofylline of -1.5 (-4.1, 1.1)mmHg at Hour 4 and -3.5 mmHg (95% CI: -6.2, -0.2) at Hour 8. There was a significant increase with rolofylline in diuresis [placebo-corrected mean (95% CI) change of 68 (20, 116)mL/h at Hour 2-4 and 103 (21, 185)mL/h at Hour 4-8] and in fractional excretion of sodium, potassium, and uric acid. Placebo-corrected changes in plasma levels of creatinine and BUN with rolofylline were non-significant.
  
  
  
  Single administration of rolofylline in patients with HF and impaired renal function produced a slight decrease in mean PAP and consistently increased diuresis and natriuresis without compromising renal function, both before and after administration of i.v. loop diuretics.
authors.affiliation: Department of Heart Diseases, Medical University, Clinical Military Hospital, Weigla 5, Wroclaw, Poland. piotrponikowski@4wsk.pl
authors.forename: Piotr
authors.initials: P
authors.lastname: Ponikowski
authors.forename: Veselin
authors.initials: V
authors.lastname: Mitrovic
authors.forename: Christopher M
authors.initials: CM
authors.lastname: O'Connor
authors.forename: Howard
authors.initials: H
authors.lastname: Dittrich
authors.forename: Gad
authors.initials: G
authors.lastname: Cotter
authors.forename: Barry M
authors.initials: BM
authors.lastname: Massie
authors.forename: Michael M
authors.initials: MM
authors.lastname: Givertz
authors.forename: Erluo
authors.initials: E
authors.lastname: Chen
authors.forename: Meredith
authors.initials: M
authors.lastname: Murray
authors.forename: Beth D
authors.initials: BD
authors.lastname: Weatherley
authors.forename: Kenji P
authors.initials: KP
authors.lastname: Fujita
authors.forename: Marco
authors.initials: M
authors.lastname: Metra
mesh_terms: D000368:Aged; D004232:Diuretics / Q000008:administration & dosage / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007677:Kidney Function Tests; D016018:Least-Squares Analysis; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000627:therapeutic use; D014970:Xanthines / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D004232:Diuretics; D049994:Sodium Potassium Chloride Symporter Inhibitors; D014970:Xanthines; C073525:rolofylline