Effects of isosorbide-5-mononitrate on variceal pressure and systemic and splanchnic haemodynamics in patients with cirrhos

: 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; in=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.