LONG-TERM HEMODYNAMIC-EFFECTS OF ISOSORBIDE 5-MONONITRATE IN PATIENTS WITH CIRRHOSIS AND PORTAL-HYPERTENSION

Since it is well known that pharmacological tolerance may rapidly occur on continuous administration of organic nitrates, in this study we attempted to investigate whether isosorbide 5-mononitrate (Is-5-Mn), a long-acting vasodilator that decreases portal pressure in acute haemodynamic studies, causes a significant reduction in portal pressure following longterm oral administration. Eleven patients with cirrhosis and portal hypertension were studied prior to and following 3 months of continuous administration of Is-5-Mn, 40 mg b.i.d. The hepatic venous pressure gradient decreased significantly following long-term Is-5-Mn treatment (from 18.6 ± 3.4 to 17.2 ±3.1 mmHg; p < 0.01). This was associated with a moderate increase in hepatic blood flow. Azygos blood flow and portal blood flow did not change. There were significant decreases in mean arterial pressure (from 89.4 ± 13.7 to 82.6 ± 10.8 mmHg; p < 0.05) and heart rate (from 77 ± 10 to 73 ±10 b.p.m.; p < 0.05). In contrast, there were no changes in portal pressure or hepatic and systemic haemodynamics in a control group of 17 patients receiving placebo. Repeated nitroglycerin cross-tolerance studies in five patients receiving Is5-Mn indicated the development of a partial pharmacological tolerance (as shown by blunted haemodynamic response to nitroglycerin after long-term Is-5-Mn administration). This study shows that Is-5-Mn continues to cause a significant decrease in portal pressure during long-term therapy, with only partial pharmacological tolerance to this compound. © 1990.