Systemic and splanchnic oxygen supply-demand relationship with fenoldopam, dopamine and noradrenaline in sheep.
The effects of intravenous administration of fenoldopam (0.3-10 micrograms.kg-1.min-1), dopamine (1-10 micrograms.kg-1.min-1) and noradrenaline (0.1-1 micrograms.kg-1.min-1) on systemic and splanchnic haemodynamics and oxygen supply-demand relationship were studied in 12 chronically instrumented, sedated sheep. Fenoldopam produced dose-dependent peripheral and splanchnic vasodilatation without change in arterial blood pressure. The coeliac trunk and portal vein blood flows were particularly sensitive to fenoldopam, whereas dopamine vasodilated these vascular beds only at high doses. Renal blood flow was not influenced by dopamine or fenoldopam, but decreased by noradrenaline. Fenoldopam maintained systemic oxygen extraction constant by increasing both oxygen supply and demand, while noradrenaline and dopamine increased oxygen supply more than demand, thus decreasing oxygen extraction. Both dopamine and fenoldopam increased oxygen delivery to the splanchnic organs while noradrenaline reduced it. Splanchnic oxygen consumption decreased with noradrenaline and increased with dopamine, resulting in a conserved oxygen extraction with both drugs, whereas oxygen consumption remained constant at all doses of fenoldopam infusion (i.e. dose-dependent decreased oxygen extraction). Both noradrenaline and fenoldopam, but not dopamine, were accompanied by increased portal lactataemia. We conclude that in sheep fenoldopam is a potent and selective splanchnic vasodilator but without vasodilatator effect on the renal circulation. The portal lactataemia associated with a decreased splanchnic oxygen extraction may present a significant limitation for some clinical applications of this drug.
Schiffer
E R
ER
Division of Surgical and Anaesthesiological Investigations, University Hospital of Geneva, Switzerland.
Schwieger
I M
IM
Gosteli
P
P
Poinsot
O
O
Mentha
G
G
Morel
D R
DR
D000818:Animals; D004298:Dopamine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D018818:Fenoldopam / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D006441:Hemoglobin A / Q000032:analysis; D007773:Lactates / Q000097:blood; D009638:Norepinephrine / Q000494:pharmacology*; D010100:Oxygen / Q000097:blood*; D011652:Pulmonary Circulation / Q000187:drug effects; D012756:Sheep; D013152:Splanchnic Circulation / Q000187:drug effects* / Q000502:physiology; D013566:Sympathomimetics / Q000494:pharmacology*
D018491:Dopamine Agonists; D007773:Lactates; D013566:Sympathomimetics; D006441:Hemoglobin A; D018818:Fenoldopam; D010100:Oxygen; D004298:Dopamine; D009638:Norepinephrine