Sildenafil is valuable in the treatment of erectile dysfunction and pulmonary hypertension in patients with end-stage liver disease through inhibition of the type-5 phosphodiesterase.
The type-5 phosphodiesterase is also present in human mesenteric arteries. The effect of sildenafil on splanchnic blood flow and portal hypertension remains essentially unknown.
The research team led by Otto Clemmesen from Denmark addresses this question and this will be be published on October 28; 2008 in the World Journal of Gastroenterology.
Ten patients with biopsy proven cirrhosis (5 females/5 males, mean age 54 ± 8 years) and the hepatic venous pressure gradient (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.
They found that the plasma concentration of sildenafil was 222 ± 136 ng/mL 80 min after administration. Mean arterial blood pressure decreased from 77 ± 7 to 66 ± 12 mmHg, P = 0.003, while the splanchnic blood flow and oxygen consumption remained unchanged at 1.1 ± 0.71 L/min and 2.3 ± 0.6 mmol/min, respectively. Also the HVPG remained unchanged (18 ± 2 vs 16 ± 2 mmHg) with individual changes ranging from -8 to +2 mmHg. In 7 patients HVPG decreased and in 3 it increased.
The result indicated that sildenafil do not induce any profound clinically relevant changes in splanchnic blood flow, oxygen consumption and HVPG in patients with cirrhosis. Phosphodiesterase type-5 inhibition is of no use as a therapeutic agent for alleviating portal hypertension in patients with chronic end-stage liver disease.