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World J Gastroenterol. Oct 28, 2008; 14(40): 6208-6212
Published online Oct 28, 2008. doi: 10.3748/wjg.14.6208
Sildenafil does not influence hepatic venous pressure gradient in patients with cirrhosis
Jens Otto Clemmesen, Annamaria Giraldi, Peter Ott, Kim Dalhoff, Bent Adel Hansen, Fin Stolze Larsen
Jens Otto Clemmesen, Peter Ott, Bent Adel Hansen, Fin Stolze Larsen, Department of Hepatology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen DK-2100, Denmark
Annamaria Giraldi, Kim Dalhoff, Clinical Pharmacology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen DK-2100, Denmark
Author contributions: Clemmesen JO, Giraldi A, Ott P, and Dalhoff K designed research; Clemmesen JO performed research; Dalhoff K contributed with analytic tools; Clemmesen JO and Ott P analyzed data; Clemmesen JO, Ott P, Hansen BA, and Larsen FS wrote the paper.
Supported by Rigshospitalet, University of Copenhagen, The Laerdal Foundation for Acute Medicine; Savvaerksejer Jeppe Juhl and wife Ovita Juhls Foundation; The Novo Nordisk Foundation; The AP-Møller Foundation; and an unrestricted grant from Pfizer, Denmark
Correspondence to: Jens Otto Clemmesen, MD, DMSc, Department of Hepatology A-2121, Rigshospitalet, Blegdamsvej 9, Copenhagen DK-2100, Denmark. otto.clemmesen@rh.regionh.dk
Telephone: +45-35-450596 Fax: +45-35-452913
Received: December 8, 2007
Revised: July 26, 2008
Accepted: August 3, 2008
Published online: October 28, 2008
Abstract

AIM: To investigate if sildenafil increases splanchnic blood flow and changes the hepatic venous pressure gradient (HVPG) in patients with cirrhosis. Phosphodiesterase type-5 inhibitors are valuable in the treatment of erectile dysfunction and pulmonary hypertension in patients with end-stage liver disease. However, the effect of phosphodiesterase type-5 inhibitors on splanchnic blood flow and portal hypertension remains essentially unknown.

METHODS: Ten patients with biopsy proven cirrhosis (five females/five males, mean age 54 ± 8 years) and an HVPG above 12 mmHg were studied after informed consent. Measurement of splanchnic blood flow and the HVPG during liver vein catheterization were done before and 80 min after oral administration of 50 mg sildenafil. Blood flow was estimated by use of indocyanine green clearance technique and Fick's principle, with correction for non-steady state.

RESULTS: The plasma concentration of sildenafil was 222 ± 136 ng/mL 80 min after administration. Mean arterial blood pressure decreased from 77 ± 7 mmHg to 66 ± 12 mmHg, P = 0.003, while the splanchnic blood flow and oxygen consumption remained unchanged at 1.14 ± 0.71 L/min and 2.3 ± 0.6 mmol/min, respectively. Also the HVPG remained unchanged (18 ± 2 mmHg vs 16 ± 2 mmHg) with individual changes ranging from -8 mmHg to +2 mmHg. In seven patients, HVPG decreased and in three it increased.

CONCLUSION: In spite of arterial blood pressure decreases 80 min after administration of the phosphodiesterase type-5 inhibitor sildenafil, the present study could not demonstrate any clinical relevant influence on splanchnic blood flow, oxygen consumption or the HVPG.

Keywords: Cirrhosis, Sildenafil, Portal hypertension, Portal hemodynamics, Hepatic blood flow, Erectile dysfunction, Hepatic venous pressure gradient