Bolus somatostatin but not octreotide reduces hepatic sinusoidal pressure by a NO-independent mechanism in chronic liver disease

Abstract

Background: Evidence exists that somatostatin and octreotide might have different effects on hepatic haemodynamics.

Aim: The investigation of the effects of somatostatin and its octapeptide analogue, octreotide, on sinusoidal pressure measured by the wedged hepatic venous pressure in patients with cirrhosis or chronic hepatitis and the correlation with the levels of hepatic vein NO.

Methods: Patients were randomly assigned to receive an injection of either 250 microg somatostatin (n=14: cirrhosis six, chronic hepatitis eight) or an injection of 125 microg octreotide (n=19: cirrhosis nine, chronic hepatitis 10) during hepatic vein catheterization. Baseline wedged hepatic venous pressure was measured, followed by measurements at 2, 5, 10 and 15 min after the injection of the drug. Nitrites/nitrates of the hepatic vein were measured before the injection and after 15 min.

Results: Both agents showed a similar qualitative but a different quantitative haemodynamic profile. No change in the wedged hepatic venous pressure was observed during the first 2 min after the injection of both drugs. This was followed by a decrease: 18% at 5 min (N.S.), 23% at 10 min (P < 0.01) and 24% at 15 min (P < 0.01) for somatostatin. Octreotide induced a relatively smaller decrease in the wedged hepatic venous pressure: 8% at 5 min (N.S.), 20% at 10 min (P < 0.01) and 16% at 15 min (N.S.). Further analysis of the sub-groups of cirrhotic and chronic hepatitis patients revealed a different effect. In the sub-group of cirrhotic patients, somatostatin caused a maximum decrease of 34% at 15 min post-injection (P < 0.01), but octreotide failed to produce a significant change on the wedged hepatic venous pressure. In contrast, no change was observed in chronic hepatitis patients with either drug. No change in the hepatic vein concentration of NO after treatment was observed with either somatostatin or octreotide. Moreover, no correlation of the levels of NO with the wedged hepatic venous pressure values was found.

Conclusions: This study shows that somatostatin is more effective than octreotide in acutely reducing the wedged hepatic venous pressure after bolus injection and the observed change is probably mediated by a NO-independent mechanism.