title: Plasma clearances and extractions of four catecholamines in the anesthetized rabbit: the role of amine removal by blood cells.
abstract: The purpose of the present study was to compare the plasma kinetics of norepinephrine (NA), epinephrine (A), isoprenaline (ISO), and dopamine (DA) in the anesthetized rabbit. To this end, a mixture of trace amounts of 3H-labeled NA, A, ISO, and DA was infused either into a femoral vein or into the ascending aorta, and the plasma amine clearances (Cl), the fractional amine extractions across the pulmonary (ERp) as well as systemic (ERs) circulation, and the cardiac output of plasma (COp) were determined at steady state of the amine infusion. The values of ERp, ERs, and COp were also used to calculate total-body fractional extractions [ERtot = ERp + ERs(1 - ERp)] and theoretical clearances (Clcalc = ERtot * COp). The four catecholamines differed as to their values of Cl and ERs and even more so with respect to ERp. The Cl was lowest for NA, intermediate for A and ISO, and highest for DA. Statistically significant pulmonary extractions were observed for NA (8.8%) and DA (24.0%), but not for A and ISO. The systemic extraction was lowest for ISO (63%) and highest for DA (75%). Cl values were higher than values of Clcalc and the ratio of Cl/Clcalc increased in the order of NA < A < ISO < DA. In vitro experiments, in which whole rabbit blood was incubated in the presence of added NA, A, ISO, and DA, showed a pronounced ability of blood cells to remove catecholamines from plasma. The four amines rapidly disappeared from plasma at rates increasing in the order of NA < A < ISO < DA.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology and Toxicology, University of Würzburg, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Friedgen
authors.forename: T
authors.initials: T
authors.lastname: Halbrügge
authors.forename: K H
authors.initials: KH
authors.lastname: Graefe
mesh_terms: D000818:Animals; D001773:Blood Cells / Q000378:metabolism*; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000494:pharmacology; D004298:Dopamine / Q000097:blood* / Q000493:pharmacokinetics; D004837:Epinephrine / Q000097:blood* / Q000493:pharmacokinetics; D005268:Femoral Vein; D066298:In Vitro Techniques; D007262:Infusions, Intravenous; D007545:Isoproterenol / Q000097:blood* / Q000493:pharmacokinetics; D008297:Male; D009638:Norepinephrine / Q000097:blood* / Q000493:pharmacokinetics; D011652:Pulmonary Circulation; D011817:Rabbits
chemical_list: D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D007545:Isoproterenol; C057726:OR486; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine