title: Selective dopamine DA1 stimulation with fenoldopam in cirrhotic patients with ascites: a systemic, splanchnic and renal hemodynamic study.
abstract: We studied the effects of fenoldopam, a selective dopamine DA1 agonist on systemic and splanchnic hemodynamics, renal blood flow and sodium excretion in 12 patients with alcoholic cirrhosis and ascites. Hepatic, azygos and renal veins were catheterized before and after intravenous administration of fenoldopam, 0.05 micrograms/kg/min for 1 hr and increased to 0.1 micrograms/kg/min for another hour. Mean arterial pressure progressively decreased (from 83 +/- 7 to a minimum of 77 +/- 8 mm Hg 100 min after starting the infusion) but returned to baseline level at 120 min. Plasma norepinephrine and renin activity increased (respectively from 567 +/- 297 to 919 +/- 375 pg/ml, p less than 0.05, and from 17 +/- 14 to 23 +/- 15 ng/ml/hr, p less than 0.05). Renal blood flow, urine output or sodium excretion did not change. Sodium output decreased at 1 hr from 6.9 mumol/min to 4.0 mumol/min, p less than 0.05. Both hepatic venous pressure gradient and azygos blood flow significantly increased by 21%. We conclude that the acute administration of fenoldopam did not improve renal hemodynamics or function in patients with cirrhosis and ascites. In addition, dopamine DA1 agonism caused further increases in norepinephrine concentration and plasma renin activity. Portal pressure also increased, probably because of an increase in mesenteric blood flow. These results question the renal benefit and raise concern about the use of dopamine agonists in patients with cirrhosis and ascites.
authors.affiliation: Unité de Recherches de Physiopathologie Hépatique (INSERM U 24), Hôpital Beaujon, France.
authors.forename: A
authors.initials: A
authors.lastname: Hadengue
authors.forename: R
authors.initials: R
authors.lastname: Moreau
authors.forename: Y
authors.initials: Y
authors.lastname: Bacq
authors.forename: C
authors.initials: C
authors.lastname: Gaudin
authors.forename: A
authors.initials: A
authors.lastname: Braillon
authors.forename: D
authors.initials: D
authors.lastname: Lebrec
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000328:Adult; D001201:Ascites / Q000503:physiopathology*; D015259:Dopamine Agents / Q000494:pharmacology*; D018818:Fenoldopam; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D008102:Liver Circulation / Q000187:drug effects; D008103:Liver Cirrhosis / Q000503:physiopathology*; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D011954:Receptors, Dopamine / Q000187:drug effects*; D017447:Receptors, Dopamine D1; D012079:Renal Circulation / Q000187:drug effects; D013152:Splanchnic Circulation / Q000187:drug effects
chemical_list: D015259:Dopamine Agents; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D018818:Fenoldopam; D009638:Norepinephrine