THE ACUTE AND CHRONIC EFFECTS OF ISOSORBIDE-5-MONONITRATE ON PORTAL HEMODYNAMICS IN CIRRHOSIS

The effects of acute and chronic administration of isosorbide-5-mononi trate on portal and systemic circulation was studied in patients with cirrhosis and portal hypertension. Acute administration reduced the me an 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 f low. The hepatic venous pressure gradient fell consistently only in pa tients in whom the azygos blood flow increased acutely. With chronic a dministration no reduction in mean arterial and hepatic venous pressur e gradient was identified before rechallenge, despite a marked and con sistent reduction in azygos flow (540+/-89 to 306+/-60 ml/min). Rechal lenge with isosorbide-5-mononitrate in patients on chronic nitrate the rapy reproduced the haemodynamic effects identified with acute adminis tration, lowering mean arterial and hepatic venous pressure gradient ( 19+/-1.5 to 16.0+/-1.8 mmHg) with a variable effect on azygos flow. Th e wedged hepatic venous pressure was significantly lower than pretreat ment values (19.9+/-1.6 compared with 23.4+/-2.1 mmHg). We conclude th at acute nitrate administration lowers the hepatic venous pressure gra dient, either by reducing portal venous inflow or by reducing portal-c ollateral resistance. Chronic administration reduces portal-collateral flow without consistently lowering the hepatic venous pressure gradie nt. No evidence of nitrate tolerance or tachyphylaxis was observed. (C ) Journal of Hepatology.