Oral administration of nipradilol and the acute and chronic splanchnic hemodynamic effects of a new beta-blocker with nitrovasodilating properties in patients with liver cirrhosis

Abstract

Objectives: We studied the effects of nipradilol, which has both a nonselective beta-blocker action and a vasodilating action similar to nitroglycerin, on portal hypertension.

Methods: We measured hepatic venous pressure gradient and splanchnic and systemic hemodynamics before beginning therapy, 2 h after an oral dose of 6 mg, and after either 6 months of nipradilol 6 mg twice a day (n = 14) or of a placebo (n = 6) in 20 cirrhotic patients.

Results: No significant changes were observed after the administration of the placebo. Oral nipradilol induced a significant reduction in the hepatic venous pressure gradient (base line: 14.8 +/- 3.2 mm Hg vs 2 h: 12.3 +/- 3.4 mm Hg, p < 0.01; 6 mo: 12.5 +/- 3.2 mm Hg, p < 0.05) without a significant change in the free hepatic venous pressure. The hepatic vascular resistance decreased significantly (base line: 1811 +/- 778 dyn.sec.cm-5 vs 2 h: 1540 +/- 701 dyn.sec.cm-5, p < 0.05; 6 mo: 1564 +/- 693 dyn.sec.cm-5, p < 0.05) without a significant change in hepatic blood flow. A decrease in the hepatic venous pressure gradient greater than 10% was observed in nine patients (64%), defined as "responders," at 2 h and in 10 patients (71%) at 6 months. The reduction of mean heart rate and hepatic venous pressure gradient in these responders was 16.2% and 28.3% at 2 h and 15.1% and 27.1% at 6 months, respectively.

Conclusions: We found that in some cirrhotic patients, at the doses used in this study, long term oral nipradilol administration produces a reduction in the hepatic venous pressure gradient with both a beta-blocking and a nitrovasodilating action.