Increased sympathetic nervous activity and the effects of its inhibition with clonidine in alcoholic cirrhosis.
OBJECTIVE
To study disturbances in sympathetic nervous system function in patients with alcoholic cirrhosis and the effect of clonidine on such disturbances.


METHODS
Cross-sectional physiologic and neurochemical evaluation of patients with cirrhosis and of healthy controls; an uncontrolled trial of intravenous clonidine in the cirrhotic patients.


METHODS
Forty-four hospitalized patients with biopsy-proven alcoholic cirrhosis and 31 healthy controls.


METHODS
Intravenous clonidine.


METHODS
Radiotracer-derived measures of norepinephrine release to plasma, central hemodynamics, wedge hepatic vein pressure, and measures of renal function.


RESULTS
In patients with cirrhosis, clonidine reduced previously elevated norepinephrine overflow rates for the whole body, kidneys, and hepatomesenteric circulation. This sympathetic inhibition was accompanied by the following potentially clinically beneficial effects: the lowering of renal vascular resistance (median reduction, 24%; 95% CI, 14% to 31%), the elevation of glomerular filtration rate (median increase, 27%; CI, 14% to 39%), and the reduction of portal venous pressure (median reduction, 25%; CI, 18% to 32%). The norepinephrine and hemodynamic responses to graded clonidine dosing (1, 2, and 3 micrograms/kg body weight intravenously) indicated that the sympathetic outflow to the hepatomesenteric circulation was more sensitive to pharmacologic suppression with clonidine than was the sympathetic outflow to the systemic circulation.


CONCLUSIONS
The sympathetic nerves to the kidneys, heart, and hepatomesenteric circulation are stimulated in patients with cirrhosis. Clonidine inhibits these activated sympathetic outflows differentially, which could possibly provide a basis for the selective pharmacologic treatment of portal hypertension in patients with cirrhosis.
Esler
M
M
Alfred Hospital, Prahran, Australia.
Dudley
F
F
Jennings
G
G
Debinski
H
H
Lambert
G
G
Jones
P
P
Crotty
B
B
Colman
J
J
Willett
I
I
D000328:Adult; D000368:Aged; D003000:Clonidine / Q000494:pharmacology*; D003430:Cross-Sectional Studies; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D011169:Portal Vein / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D014690:Venous Pressure / Q000187:drug effects
D003000:Clonidine; D009638:Norepinephrine