Literature DB >> 20144739

Sildenafil has no effect on portal pressure but lowers arterial pressure in patients with compensated cirrhosis.

Puneeta Tandon1, Irteza Inayat, Michael Tal, Marcelo Spector, Martha Shea, Roberto J Groszmann, Guadalupe Garcia-Tsao.   

Abstract

BACKGROUND & AIMS: The reduction of portal pressure in patients with early compensated cirrhosis may be more responsive to drugs increasing intrahepatic vasodilatation than those reducing portal venous inflow. The phosphodiesterase-5 (PDE-V) inhibitor sildenafil can potentially reduce portal pressure by decreasing intrahepatic resistance, but its systemic vasodilatory effects may be deleterious. The aim of this study was to evaluate the effect of sildenafil on systemic and portal hemodynamics in an open-label pilot study.
METHODS: Twelve patients with compensated cirrhosis and baseline hepatic venous pressure gradient (HVPG) >5 mm Hg received 25 mg of oral sildenafil. Mean arterial pressure (MAP), heart rate (HR), and HVPG were repeated after 30 and 60 minutes in 9/12 patients at 90 minutes (after an additional 25 mg of sildenafil). HVPG tracings were read by 3 blinded observers.
RESULTS: All 12 patients were Child A with median MAP of 92 mm Hg (interquartile range, 83-94) and HVPG 10.4 mm Hg (interquartile range, 6.6-13.0). While MAP decreased significantly at all time points, sildenafil had no effect on HVPG.
CONCLUSIONS: As shown with other vasodilators in compensated cirrhotic patients, sildenafil at therapeutic doses for erectile dysfunction reduces MAP without reducing portal pressure. The search should continue for specific intrahepatic vasodilators. Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

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Year:  2010        PMID: 20144739      PMCID: PMC2879450          DOI: 10.1016/j.cgh.2010.01.017

Source DB:  PubMed          Journal:  Clin Gastroenterol Hepatol        ISSN: 1542-3565            Impact factor:   11.382


  19 in total

1.  Ca/CaM-stimulated and cGMP-specific phosphodiesterases in vascular and non-vascular tissues.

Authors:  H S Ahn; M Foster; M Cable; B J Pitts; E J Sybertz
Journal:  Adv Exp Med Biol       Date:  1991       Impact factor: 2.622

2.  Inhibition of cGMP-specific phosphodiesterase type 5 reduces sodium excretion and arterial blood pressure in patients with NaCl retention and ascites.

Authors:  Helle C Thiesson; Boye L Jensen; Bente Jespersen; Ove B Schaffalitzky de Muckadell; Claus Bistrup; Steen Walter; Peter D Ottosen; Annegrete Veje; Ole Skøtt
Journal:  Am J Physiol Renal Physiol       Date:  2004-12-21

3.  Evidence for expression and function of phosphodiesterase type 5 (PDE-V) in rat resistance arteries.

Authors:  L J Sampson; J M Hinton; C J Garland
Journal:  Br J Pharmacol       Date:  2001-01       Impact factor: 8.739

Review 4.  Molecular mechanism of cGMP-mediated smooth muscle relaxation.

Authors:  J A Carvajal; A M Germain; J P Huidobro-Toro; C P Weiner
Journal:  J Cell Physiol       Date:  2000-09       Impact factor: 6.384

5.  Relaxation induced by cGMP phosphodiesterase inhibitors sildenafil and zaprinast in human vessels.

Authors:  P Medina; G Segarra; J B Martínez-León; J M Vila; M Aldasoro; E Otero; S Lluch
Journal:  Ann Thorac Surg       Date:  2000-10       Impact factor: 4.330

6.  Sildenafil does not influence hepatic venous pressure gradient in patients with cirrhosis.

Authors:  Jens-Otto Clemmesen; Annamaria Giraldi; Peter Ott; Kim Dalhoff; Bent-Adel Hansen; Fin-Stolze Larsen
Journal:  World J Gastroenterol       Date:  2008-10-28       Impact factor: 5.742

7.  Pharmacological reduction of portal pressure and long-term risk of first variceal bleeding in patients with cirrhosis.

Authors:  Juan Turnes; Juan Carlos Garcia-Pagan; Juan G Abraldes; Manuel Hernandez-Guerra; Alessandra Dell'Era; Jaime Bosch
Journal:  Am J Gastroenterol       Date:  2006-03       Impact factor: 10.864

8.  Increased phosphodiesterase-5 expression is involved in the decreased vasodilator response to nitric oxide in cirrhotic rat livers.

Authors:  Mauricio R Loureiro-Silva; Yasuko Iwakiri; Juan G Abraldes; Omar Haq; Roberto J Groszmann
Journal:  J Hepatol       Date:  2006-02-28       Impact factor: 25.083

9.  Acute administration of sildenafil enhances hepatic cyclic guanosine monophosphate production and reduces hepatic sinusoid resistance in cirrhotic patients.

Authors:  Kuei-Chuan Lee; Ying-Ying Yang; Ying-Wen Wang; Ming-Chih Hou; Fa-Yauh Lee; Han-Chieh Lin; Shou-Dong Lee
Journal:  Hepatol Res       Date:  2008-07-04       Impact factor: 4.288

10.  Rapid nitric oxide-induced desensitization of the cGMP response is caused by increased activity of phosphodiesterase type 5 paralleled by phosphorylation of the enzyme.

Authors:  F Mullershausen; M Russwurm; W J Thompson; L Liu; D Koesling; A Friebe
Journal:  J Cell Biol       Date:  2001-10-15       Impact factor: 10.539

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  12 in total

1.  Haemodynamic and renal effects of tadalafil in patients with cirrhosis.

Authors:  Georgios N Kalambokis; Paraskevi Kosta; Konstantinos Pappas; Epameinondas V Tsianos
Journal:  World J Gastroenterol       Date:  2010-10-21       Impact factor: 5.742

2.  Prevalence and risk factors of erectile dysfunction in patients with liver cirrhosis: a systematic review and meta-analysis.

Authors:  Hye Jin Yoo; Bora Lee; Eun-Ae Jung; Sang Gyune Kim; Young Seok Kim; Jeong-Ju Yoo
Journal:  Hepatol Int       Date:  2021-11-20       Impact factor: 6.047

3.  Does Treatment of Erectile Dysfunction With PDE 5 Inhibitor Tadalafil Improve Quality of Life in Male Patients With Compensated Chronic Liver Disease? A Prospective Pilot Study.

Authors:  Alok Kumar; Vivek Saraswat; Gaurav Pande; Rajesh Kumar
Journal:  J Clin Exp Hepatol       Date:  2022-01-23

4.  Future Pharmacological Therapies of Portal Hypertension.

Authors:  Guillermo A Ortiz; Guadalupe Garcia-Tsao
Journal:  Curr Hepatol Rep       Date:  2019-02-19

5.  Tadalafil, a Phosphodiesterase-5 Inhibitor, Improves Erectile Dysfunction in Patients With Liver Cirrhosis.

Authors:  Jitender Thakur; Sahaj Rathi; Sandeep Grover; Madhu Chopra; Swastik Agrawal; Sunil Taneja; Ajay Duseja; Anil Bhansali; Yogesh K Chawla; Radha K Dhiman
Journal:  J Clin Exp Hepatol       Date:  2018-08-18

6.  Novel treatment options for portal hypertension.

Authors:  Philipp Schwabl; Wim Laleman
Journal:  Gastroenterol Rep (Oxf)       Date:  2017-04-18

7.  Erectile dysfunction in cirrhosis is impacted by liver dysfunction, portal hypertension, diabetes and arterial hypertension.

Authors:  Rafael Paternostro; Birgit B Heinisch; Thomas Reiberger; Mattias Mandorfer; Remy Schwarzer; Berit Seeland; Michael Trauner; Markus Peck-Radosavljevic; Arnulf Ferlitsch
Journal:  Liver Int       Date:  2018-02-20       Impact factor: 5.828

8.  Beneficial long term effect of a phosphodiesterase-5-inhibitor in cirrhotic portal hypertension: A case report with 8 years follow-up.

Authors:  Peter Deibert; Adhara Lazaro; Zoran Stankovic; Denise Schaffner; Martin Rössle; Wolfgang Kreisel
Journal:  World J Gastroenterol       Date:  2018-01-21       Impact factor: 5.742

9.  Analysis of the nitric oxide-cyclic guanosine monophosphate pathway in experimental liver cirrhosis suggests phosphodiesterase-5 as potential target to treat portal hypertension.

Authors:  Denise Schaffner; Adhara Lazaro; Peter Deibert; Peter Hasselblatt; Patrick Stoll; Lisa Fauth; Manfred W Baumstark; Irmgard Merfort; Annette Schmitt-Graeff; Wolfgang Kreisel
Journal:  World J Gastroenterol       Date:  2018-10-14       Impact factor: 5.742

Review 10.  Phosphodiesterases in the Liver as Potential Therapeutic Targets of Cirrhotic Portal Hypertension.

Authors:  Wolfgang Kreisel; Denise Schaffner; Adhara Lazaro; Jonel Trebicka; Irmgard Merfort; Annette Schmitt-Graeff; Peter Deibert
Journal:  Int J Mol Sci       Date:  2020-08-28       Impact factor: 5.923

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