title: Effect of clonidine on liver oxygen extraction during alcohol withdrawal in man.
abstract: Since catecholamines can alter splanchnic oxygen transport and extraction, the suppression of sympathetic overactivity during alcohol withdrawal might improve hepatic oxygen extraction. Therefore, this study investigated the effects of clonidine, a centrally-acting alpha 2-agonist which reduces sympathetic nervous outflow, on splanchnic oxygen transport and extraction in 13 patients with chronic alcoholism during alcohol withdrawal. All patients had elevated transaminases and steatosis at liver biopsy and were withdrawn from alcohol 51 +/- 15 h (mean +/- SD) before the study. Hepatic blood flow, cardiac output and the oxygen contents were measured in the radial and pulmonary arteries and in the hepatic veins before and 45 min after intravenous administration of clonidine, 150 micrograms. Basal hepatic blood flow was inversely correlated with norepinephrine plasma concentrations (r = -0.63, p < 0.025). After clonidine administration, the decrease in plasma norepinephrine correlated with the norepinephrine basal value (r = 0.889, p < 0.001), and splanchnic oxygen extraction increased (from 40 +/- 15 to 49 +/- 17%, p < 0.025). After clonidine administration, splanchnic oxygen extraction was correlated with the decrease in plasma norepinephrine (r = 0.72, p < 0.01). Arterial lactate concentration decreased (from 0.74 +/- 0.20 to 0.64 +/- 0.23 mmol/l, p < 0.01). These results suggest that defective liver oxygen extraction might occur during alcohol withdrawal as a result of sympathetic nervous hyperactivity. Alterations in the hepatic microcirculation during withdrawal might be related to catecholamine secretion and be controlled by pharmacological manipulation.
authors.affiliation: Service d'Hépatologie (INSERM U24), Hôpital Beaujon, Clichy, France.
authors.forename: A
authors.initials: A
authors.lastname: Hadengue
authors.forename: R
authors.initials: R
authors.lastname: Moreau
authors.forename: D
authors.initials: D
authors.lastname: Lebrec
authors.forename: C
authors.initials: C
authors.lastname: Gaudin
authors.forename: B
authors.initials: B
authors.lastname: Rueff
authors.forename: J P
authors.initials: JP
authors.lastname: Benhamou
mesh_terms: D000328:Adult; D003000:Clonidine / Q000494:pharmacology*; D000431:Ethanol / Q000009:adverse effects*; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008102:Liver Circulation; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D010100:Oxygen / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
chemical_list: D000431:Ethanol; D003000:Clonidine; D010100:Oxygen; D009638:Norepinephrine