BACKGROUND: Dysregulation of the cyclic guanosine 3',5' monophosphate-nitric oxide system is in part responsible for portal hypertension in cirrhosis. AIM: 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.
BACKGROUND: Dysregulation of the cyclic guanosine 3',5' monophosphate-nitric oxide system is in part responsible for portal hypertension in cirrhosis. AIM: To test the effects of inhibitors of phosphodiesterase-5 on portal haemodynamics. METHODS: To 18 healthy subjects and 18 patients with ChildA 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: Ayse L Mindikoglu; Thomas C Dowling; David J Schaub; William R Hutson; Darryn R Potosky; Robert H Christenson; Rolf N Barth; John C LaMattina; Steven I Hanish; Matthew R Weir; Jean-Pierre Raufman Journal: Dig Dis Sci Date: 2015-07-05 Impact factor: 3.199
Authors: Ksenia Brusilovskaya; Philipp Königshofer; Daniel Lampach; Adrian Szodl; Paul Supper; David Bauer; Andrea Beer; Judith Stift; Gerald Timelthaler; Georg Oberhuber; Bruno Karl Podesser; Martha Seif; Kerstin Zinober; Nataliya Rohr-Udilova; Michael Trauner; Thomas Reiberger; Philipp Schwabl Journal: United European Gastroenterol J Date: 2020-09-02 Impact factor: 4.623