Ketanserin, a 5-hydroxytryptamine-2 receptor blocker, has been shown to decrease portal pressure in recent acute hemodynamic studies that have been performed both in experimental animals and portal hypertensive patients. The present study was designed to investigate the effects of chronic oral administration of ketanserin in portal hypertensive patients with cirrhosis. The mean baseline hepatic venous pressure gradient in the 13 patients with alcoholic cirrhosis who completed the study was 15.7 f 2.7 mmHg. It decreased significantly to 13.3 2 2.0 mmHg (p < 0.001) after ketanserin was administered at a mean dose of 51 mg per day for a mean period of 32 days. This 14.6% reduction in hepatic venous pressure gradient resulted mainly from a decrease in mean wedged hepatic venous pressure (from 22.2 2 4.0 to 20.1 f 3.6 mmHg) and was accompanied by significant decreases in cardiac index (18.8%) and in mean arterial pressure (8.1%). However, changes in cardiac index or in mean arterial pressure were not predictive of modifications in the hepatic venous pressure gradient. Eight of 16 patients entered in the study developed side effects, the most significant being a reversible portosystemic encephalopathy, which occurred in three patients who had poor liver function.
This study confirms evidence in favor of a role for 5hydroxytryptamine in portal hypertension and adds a new group of agents for the chronic treatment of portal hypertensive patients.
Although the long-term oral administration of ketanserin reduces the mean portal pressure in patients with alcoholic cirrhosis and portal hypertension, the high incidence of side effects may limit its value, especially in patients who have a poor liver function.
Portal hypertension results from both an increase in portal venous resistance and in portal blood flow. Therefore, substances that decrease resistance to portal flow (vasodilators) or decrease inflow into the portal system (vasoconstrictors) have been used experimentally and therapeutically in the treatment of portal hypertension (1).
5-Hydroxytryptamine (5HT) is a powerful venoconstrictor that has been shown to increase portal venous