HEMODYNAMIC-EFFECTS OF ALPHA-ADRENERGIC BLOCKADE WITH PRAZOSIN IN CIRRHOTIC-PATIENTS WITH PORTAL-HYPERTENSION

This study was aimed at investigating whether the blockade of alpha(1)-adrenergic receptors could reduce portal pressure in cirrhosis. Splanchnic and systemic hemodynamics were measured in 12 cirrhotic patients with esophageal varices at baseline and 1 hr after oral administration of 2 mg of prazosin (acute study). Measurements were repeated in 10 of these 12 patients after a 3-mo course of 5 mg/12 hr of prazosin (long-term study). Short-term prazosin significantly lowered the hepatic venous pressure gradient from 20.1 +/- 1.3 to 14.4 +/- 0.9 mm Hg (-25.7%) (p < 0.01), and chronic prazosin reduced it to 16.5 +/- 1.3 mm Hg (-19.1%) (p < 0.01). Hepatic blood how was increased, thus changes in the hepatic venous pressure gradient resulted from a reduction in the estimated hepatic vascular resistance. Reductions in hepatic venous pressure gradient achieved after short-term and long-term prazosin were not significantly different. Reductions in mean arterial pressure and systemic vascular resistance were significantly greater after short-term than after long-term prazosin. Long-term prazosin was associated with significant increases in hepatic and intrinsic hepatic clearances of indocyanine green. This therapy also led to an increase in pulmonary capillary pressure (+28.6%, p < 0.05) and body weight (+3.06%, p < 0.01) and a decrease in hematocrit (-6.1%, p < 0.05) and urinary sodium excretion (-22.6%, p < 0.05). In contrast, there were no hemodynamic changes in a group of six cirrhotic patients receiving placebo. In cirrhotic patients, short-term prazosin lowers portal pressure by decreasing hepatic vascular resistance. These changes are maintained during long-term therapy, being associated with an improvement in liver function tests. Although attenuated, the arterial vasodilator effect of short-term prazosin persists during long-term therapy and seems to enhance fluid retention.