title: Vascular and extravascular volume expansion of dobutamine and norepinephrine in normovolemic sheep.
abstract: In low-flow states, such as circulatory shock, both fluids and catecholamines are often coadministered. We have previously found that adrenergic agents alter volume expansion after a fluid bolus. The present study tested the volume expansion properties of dobutamine and norepinephrine in sheep treated with (series 1) and without (series 2) a fluid bolus. Series 1 (n = 6 per group): no drug (control), dobutamine (10 μg x kg(-1) x min), or norepinephrine (1.0 μg x kg(-1) x min(-1)) was begun 30 min before a 24-mL x kg(-1), 20-min, 0.9% NaCl bolus. The effect of drug and fluid on plasma volume (ΔPV), urinary output (UOP), and extravascular volume (ΔEVV) was determined. Series 2: Identical protocol but no fluid bolus. Series 1: the fluid bolus resulted in a peak and sustained ΔPV expansion. Norepinephrine (7.5 ± 0.9 mL x kg(-1)) and dobutamine (9.5 ± 1.1 mL x kg(-1)) significantly increased ΔPV compared with control (3.8 ± 1.1 mL x kg(-1)). Cumulative UOP was reduced by dobutamine (3.8 ± 1.4 mL x kg) compared with norepinephrine (25.1 ± 3.9 mL x kg(-1)) and control (16.9 ± 4.0 mL x kg(-1)). Norepinephrine increased ΔPV, while reducing ΔEVV after bolus. Series 2: ΔPV was unchanged in the control group. Dobutamine and norepinephrine increased ΔPV over time, 5.1 ± 0.5 and 4.0 ± 0.5 mL x kg(-1), respectively. At study end, UOP was lowest in dobutamine. Norepinephrine resulted in loss of ΔEVV fluid. data suggest a novel role for adrenergic receptors in regulating vascular and EVV expansion. β-Adrenergic agonists enhance vascular volume expansion, whereas α-adrenergic agonists eliminate extravascular fluid.
authors.affiliation: University of Texas Medical Branch, Galveston, Texas 77555, USA.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Stephens
authors.forename: Nabeel
authors.initials: N
authors.lastname: Uwaydah
authors.forename: George C
authors.initials: GC
authors.lastname: Kramer
authors.forename: Donald S
authors.initials: DS
authors.lastname: Prough
authors.forename: Michael
authors.initials: M
authors.lastname: Salter
authors.forename: Michael P
authors.initials: MP
authors.lastname: Kinsky
mesh_terms: D000322:Adrenergic Agonists / Q000627:therapeutic use; D000316:Adrenergic alpha-Agonists / Q000627:therapeutic use; D000318:Adrenergic beta-Agonists / Q000627:therapeutic use; D000818:Animals; D004280:Dobutamine / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D005440:Fluid Therapy; D006439:Hemodynamics / Q000187:drug effects; D009638:Norepinephrine / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010953:Plasma Volume / Q000187:drug effects; D012756:Sheep
chemical_list: D000322:Adrenergic Agonists; D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D004280:Dobutamine; D009638:Norepinephrine