Effects of isosorbide-5-mononitrate on variceal pressure and systemic and splanchnic haemodynamics in patients with cirrhosis.
BACKGROUND
Isosorbide-5-mononitrate is a long-acting nitrovasodilator which was introduced for the treatment of portal hypertension because of its capacity to reduce portal pressure. In contrast to vasoconstrictors, isosorbide-5-mononitrate acts primarily by decreasing portal-collateral resistance without deleterious effects on liver function, although at high doses, a reflex splanchnic vasoconstriction elicited by the fall in arterial pressure may further decrease portal pressure. However, there is no information on the effects of isosorbide-5-mononitrate on variceal pressure, which is thought to be a major determinant of variceal haemorrhage.


METHODS
We investigated the effects of isosorbide-5-mononitrate (40 mg, orally; n = 12) or placebo (n = 10) on variceal pressure (non-invasive endoscopic gauge) and hepatic haemodynamics in 22 patients with cirrhosis.


RESULTS
Placebo administration had no significant effects. In contrast, isosorbide-5-mononitrate significantly reduced variceal pressure (from 13.5 +/- 3.6 to 9.8 +/- 3.2 mmHg, p < 0.005). This was associated with a fall in wedged hepatic venous pressure (from 28 +/- 5.8 to 25.9 +/- 6.2 mmHg, p < 0.005), hepatic venous pressure gradient (from 20 +/- 4 to 18 +/- 4.7 mmHg, p < 0.005) and azygos blood flow (from 668 +/- 197 to 597 +/- 160 ml/min, p < 0.05), suggesting that the decrease in variceal pressure caused by isosorbide-5-mononitrate could be caused by both reductions in collateral resistance and collateral blood flow. Isosorbide-5-mononitrate moderately reduced mean arterial pressure (-13 +/- 16%; p < 0.005), its fall being directly related to the fall in hepatic venous pressure gradient (r = 0.6, p < 0.01).


CONCLUSIONS
The results of this study show that isosorbide-5-mononitrate markedly and significantly reduces variceal pressure in patients with cirrhosis and provide further support for its clinical use in the pharmacological treatment of portal hypertension.
Escorsell
A
A
Hepatic Haemodynamic Laboratory, Hospital Clínic i Provincial, University of Barcelona, Spain.
Feu
F
F
Bordas
J M
JM
García-Pagán
J C
JC
Luca
A
A
Bosch
J
J
Rodés
J
J
D000368:Aged; D001794:Blood Pressure / Q000187:drug effects*; D004311:Double-Blind Method; D004932:Esophageal and Gastric Varices / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006975:Hypertension, Portal / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008102:Liver Circulation / Q000187:drug effects; D008103:Liver Cirrhosis / Q000150:complications / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D013152:Splanchnic Circulation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000627:therapeutic use; D014690:Venous Pressure / Q000187:drug effects
D014665:Vasodilator Agents; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate