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


CONCLUSIONS
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 splanichnic blood flow, oxygen consumption or the HVPG.
Clemmesen
Jens-Otto
JO
Department of Hepatology A-2121, Rigshospitalet, Blegdamsvej 9, Copenhagen DK-2100, Denmark. otto.clemmesen@rh.regionh.dk
Giraldi
Annamaria
A
Ott
Peter
P
Dalhoff
Kim
K
Hansen
Bent-Adel
BA
Larsen
Fin-Stolze
FS
D000284:Administration, Oral; D000328:Adult; D005260:Female; D006801:Humans; D006975:Hypertension, Portal / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption / Q000187:drug effects; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D010879:Piperazines / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D011687:Purines / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D000068677:Sildenafil Citrate; D013152:Splanchnic Circulation / Q000187:drug effects*; D013450:Sulfones / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D014690:Venous Pressure / Q000187:drug effects*
D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate