title: Long-term haemodynamic effects of isosorbide 5-mononitrate in patients with cirrhosis and portal hypertension.
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.
authors: Liver Unit, Hospital Clínic i Provincial, University of Barcelona, Spain.
authors: J C
authors: JC
authors: García-Pagán
authors: F
authors: F
authors: Feu
authors: M
authors: M
authors: Navasa
authors: C
authors: C
authors: Bru
authors: L
authors: L
authors: Ruiz del Arbol
authors: J
authors: J
authors: Bosch
authors: J
authors: J
authors: Rodés
mesh_terms: D000284:Administration, Oral; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004311:Double-Blind Method; D005260:Female; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D006975:Hypertension, Portal / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects / Q000502:physiology; D008103:Liver Cirrhosis / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000494:pharmacology; D010919:Placebos / Q000008:administration & dosage; D013997:Time Factors
chemical_list: D010919:Placebos; D005996:Nitroglycerin; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate