Effect of chronic treatment with nadolol plus isosorbide mononitrate on liver blood flow and liver metabolic activity in cirrhosis.
OBJECTIVE
To assess the long-term effect of the addition of long-acting nitrates to beta-blockers on liver blood flow and liver metabolic activity in patients with cirrhosis and portal hypertension.


METHODS
Eleven patients with cirrhosis and portal hypertension were investigated by using hepatic vein catheterization and indocyanine green (ICG) constant infusion on baseline conditions, after 1 month of treatment with nadolol, after 3 months of treatment with nadolol plus isosorbide mononitrate, and (in seven cases) after 1 year of combined treatment.


RESULTS
The hepatic venous pressure gradient decreased significantly after nadolol, and more so after addition of isosorbide mononitrate. Hepatic blood flow, and ICG intrinsic hepatic clearance did not change significantly, although few cases showed an increase or decrease in either parameter. A significant correlation was found between changes in ICG intrinsic hepatic clearance and in hepatic venous pressure gradient (r = 0.62, P = 0.04).


CONCLUSIONS
Liver blood flow and liver metabolic activity are not consistently affected by addition of isosorbide mononitrate to nadolol. Substantial decreases in portal pressure may be associated with a decrease in ICG intrinsic hepatic clearance.
Merkel
C
C
Department of Clinical and Experimental Medicine, University of Padua, Italy.
Sacerdoti
D
D
Bolognesi
M
M
Buonamico
P
P
Sticca
A
A
Amodio
P
P
Angeli
P
P
Micotti
L
L
Gatta
A
A
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D004396:Coloring Agents; D003692:Delayed-Action Preparations; D004359:Drug Therapy, Combination; D005260:Female; D006503:Hepatic Veins / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007208:Indocyanine Green; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives* / Q000494:pharmacology; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D008102:Liver Circulation / Q000187:drug effects; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008875:Middle Aged; D009248:Nadolol / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D014690:Venous Pressure / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D004396:Coloring Agents; D003692:Delayed-Action Preparations; D020030:Nitric Oxide Donors; D009248:Nadolol; D007548:Isosorbide Dinitrate; D007208:Indocyanine Green; C030397:isosorbide-5-mononitrate