The acute and chronic effects of isosorbide-5-mononitrate on portal haemodynamics in cirrhosis

The effects of acute and chronic administration of isosorbide-5-mononitrate on portal and systemic circulation was studied in patients with cirrhosis and portal hypertension. Acute administration reduced the mean arterial pressure and hepatic venous pressure gradient (18.4 +/- 0.9 to 16.5 +/- 0.9 mmHg), whilst having a variable effect on azygos blood flow. The hepatic venous pressure gradient fell consistently only in patients in whom the azygos blood flow increased acutely. With chronic administration no reduction in mean arterial and hepatic venous pressure gradient was identified before rechallenge, despite a marked and consistent reduction in azygos flow (540 +/- 89 to 306 +/- 60 ml/min). Rechallenge with isosorbide-5-mononitrate in patients on chronic nitrate therapy reproduced the haemodynamic effects identified with acute administration, lowering mean arterial and hepatic venous pressure gradient (19 +/- 1.5 to 16.0 +/- 1.8 mmHg) with a variable effect on azygos flow. The wedged hepatic venous pressure was significantly lower than pretreatment values (19.9 +/- 1.6 compared with 23.4 +/- 2.1 mmHg). We conclude that acute nitrate administration lowers the hepatic venous pressure gradient, either by reducing portal venous inflow or by reducing portal-collateral resistance. Chronic administration reduces portal-collateral flow without consistently lowering the hepatic venous pressure gradient. No evidence of nitrate tolerance or tachyphylaxis was observed.