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.