Long-term sympathetic and hemodynamic responses to clonidine in patients with cirrhosis and ascites.
The aim of the present study was to examine the short- and long-term effects of the alpha 2-agonist clonidine on sympathetic overactivity, systemic, splanchnic, and renal circulation changes, and abnormal renal sodium excretion in cirrhotic patients with ascites. Of 17 patients, 8 received clonidine and 9 a placebo. Measurements were taken before and after either a single dose of clonidine (150 micrograms) and placebo or a 1-week treatment with clonidine (150 micrograms/day) and placebo. Clonidine but not placebo induced significant short- and long-term decreases in plasma norepinephrine concentrations in the pulmonary artery and the right renal vein. Acute clonidine administration induced a significant reduction in cardiac output, heart rate, arterial pressure, and hepatic venous pressure gradient but had no effect on renal hemodynamics. Long-term clonidine administration induced a significant decrease in the hepatic venous pressure gradient from 20.1 +/- 1.9 to 17.6 +/- 2.0 mm Hg (mean +/- SEM) but had no significant effects on systemic or renal hemodynamics or renal excretion of sodium. It is concluded that long-term clonidine administration in cirrhotic patients induced a sustained decrease in sympathetic nervous activity and portal pressure. In contrast, clonidine had no prolonged effect on systemic hemodynamics. In addition, short- and long-term clonidine administration did not modify renal hemodynamics or induce a natriuretic response in patients with ascites.
Roulot
D
D
Laboratoire d'Hémodynamique Splanchnique, Hôpital Beaujon, Clichy.
Moreau
R
R
Gaudin
C
C
Bacq
Y
Y
Braillon
A
A
Hadengue
A
A
Frohly
P
P
Lebrec
D
D
D001201:Ascites / Q000503:physiopathology*; D003000:Clonidine / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008103:Liver Cirrhosis / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D012079:Renal Circulation / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects*
D003000:Clonidine; D009638:Norepinephrine