Effect of vardenafil, an inhibitor of phosphodiesterase-5, on portal haemodynamics in normal and cirrhotic liver -- results of a pilot study.
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.
Deibert
P
P
Department of Preventive and Rehabilitative Sports Medicine, University Hospital Freiburg, Freiburg, Germany.
Schumacher
Y-O
YO
Ruecker
G
G
Opitz
O G
OG
Blum
H E
HE
Rössle
M
M
Kreisel
W
W
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
D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D013450:Sulfones; D014227:Triazines; D000069058:Vardenafil Dihydrochloride