Acute administration of sildenafil enhances hepatic cyclic guanosine monophosphate production and reduces hepatic sinusoid resistance in cirrhotic patients.
OBJECTIVE
In liver cirrhosis, the increased production of nitric oxide (NO) contributes to increased systemic and splanchnic vasodilatation. The inhibition of phosphodiesterase-5 (PDE-5), an enzyme responsible for the degradation of cyclic guanosine monophosphate (cGMP), is widely used in the treatment of erectile dysfunction. The aim of our study is to evaluate the overall effects of PDE-5 inhibitor administration on splanchnic, pulmonary and systemic hemodynamics in cirrhotic patients.


METHODS
Sildenafil, a specific PDE-5 inhibitor, was administrated orally to cirrhotic patients (n = 7) to see the hemodynamic changes. A control group receiving a placebo was used as a point of comparison (n = 6).


RESULTS
Compared to the control group, the hepatic vein NO and cGMP levels were significantly increased after sildenafil administration in the sildenafil group (NO from 112.3 +/- 43.5 to 325.3 +/- 117.5 nM, P = 0.018; cGMP from 7.3 +/- 0.4 to 19.2 +/- 4.2 pmol, P = 0.018). The hepatic venous pressure gradient in the sildenafil group did not differ from that of the control group. However, a significantly decreased hepatic sinusoidal resistance in the sildenafil group (1999 +/- 1243 vs. 1563 +/- 1014 dyne/s/cm(-5), P < 0.05) was noted. The study also found that the right arterial pressure, mean pulmonary arterial pressure and pulmonary capillary wedge pressure were reduced at 60 min after administration, compared with the basal parameters in cirrhotic patients receiving sildenafil (RAP1.3 +/- 2.0 vs -0.6 +/- 1.3 mmHg, MPAP 14.1 +/- 11.3 vs 11.7 +/- 9.5 mmHg, PCWP 4.6 +/- 1.7 vs 2.9 +/- 1.6 mmHg, P < 0.05 respectively).


CONCLUSIONS
An oral administration of 50 mg of sildenafil significantly decreased the mean pulmonary arterial pressure and hepatic sinusoid resistance with a significant increase in hepatic NO and cGMP production, and did not worsen portal hypertension in cirrhotic patients.
Lee
Kuei-Chuan
KC
Division of Gastroenterology, Department of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Yang
Ying-Ying
YY
Wang
Ying-Wen
YW
Hou
Ming-Chih
MC
Lee
Fa-Yauh
FY
Lin
Han-Chieh
HC
Lee
Shou-Dong
SD