title: Effect of vardenafil, an inhibitor of phosphodiesterase-5, on portal haemodynamics in normal and cirrhotic liver -- results of a pilot study.
abstract: BACKGROUND
  Dysregulation of the cyclic guanosine 3',5' monophosphate-nitric oxide system is in part responsible for portal hypertension in cirrhosis.
  
  
  OBJECTIVE
  To test the effects of inhibitors of phosphodiesterase-5 on portal haemodynamics.
  
  
  METHODS
  To 18 healthy subjects and 18 patients with Child A liver cirrhosis, 10 mg of vardenafil, an inhibitor of phosphodiesterase-5, were administered orally. Doppler sonographic measurements of hepatic and splanchnic blood flow, systemic blood pressure and heart rate were recorded before, 1 h after, and 48 h after the application. Vardenafil plasma levels were determined after 1 h. In five patients, invasive registration of free and wedged hepatic vein pressure was performed.
  
  
  RESULTS
  Portal venous flow increased in patients from 0.82 +/- 0.30 L/min (mean +/- s.d.) by 26% (CI: 16-37%, P = 0.0004) and in healthy subjects from 0.75 +/- 0.20 L/min (mean +/- s.d.) by 19% (CI: 9-28%; P = 0.0010). Celiac and hepatic artery resistivity indices rose significantly. Systemic blood pressure decreased slightly in patients. The wedged hepatic venous pressure gradient decreased in four of five patients with liver cirrhosis. Vardenafil plasma levels were higher in patients (14 +/- 10 microg/L) than in healthy subjects (9 +/- 6 microg/L; n.s.).
  
  
  CONCLUSIONS
  Inhibition of phosphodiesterase-5 increases portal flow and lowers portal pressure by a decrease in sinusoidal resistance and may be a novel therapeutic strategy for portal hypertension.
authors.affiliation: Department of Preventive and Rehabilitative Sports Medicine, University Hospital Freiburg, Freiburg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Deibert
authors.forename: Y-O
authors.initials: YO
authors.lastname: Schumacher
authors.forename: G
authors.initials: G
authors.lastname: Ruecker
authors.forename: O G
authors.initials: OG
authors.lastname: Opitz
authors.forename: H E
authors.initials: HE
authors.lastname: Blum
authors.forename: M
authors.initials: M
authors.lastname: Rössle
authors.forename: W
authors.initials: W
authors.lastname: Kreisel
mesh_terms: D000328:Adult; D001783:Blood Flow Velocity; D001794:Blood Pressure / Q000187:drug effects; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000097:blood / Q000494:pharmacology*; D008102:Liver Circulation / Q000187:drug effects*; D008103:Liver Cirrhosis / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000097:blood / Q000494:pharmacology*; D010865:Pilot Projects; D010879:Piperazines / Q000097:blood / Q000494:pharmacology*; D011168:Portal System / Q000503:physiopathology*; D013152:Splanchnic Circulation / Q000187:drug effects*; D013450:Sulfones / Q000097:blood / Q000494:pharmacology; D014227:Triazines / Q000097:blood / Q000494:pharmacology; D000069058:Vardenafil Dihydrochloride
chemical_list: D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D013450:Sulfones; D014227:Triazines; D000069058:Vardenafil Dihydrochloride