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  • Title: Long-term haemodynamic effects of isosorbide 5-mononitrate in patients with cirrhosis and portal hypertension.
    Author: García-Pagán JC, Feu F, Navasa M, Bru C, Ruiz del Arbol L, Bosch J, Rodés J.
    Journal: J Hepatol; 1990 Sep; 11(2):189-95. PubMed ID: 2123914.
    Abstract:
    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 long-term 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 less than 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 less than 0.05) and heart rate (from 77 +/- 10 to 73 +/- 10 b.p.m.; p less than 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 Is-5-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.
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