title: The alpha 2 adrenergic agonist, dexmedetomidine, selectively attenuates ischemia-induced increases in striatal norepinephrine concentrations.
abstract: This study was designed to evaluate the ability of a selective alpha 2 adrenergic agonist (dexmedetomidine) to attenuate ischemia-induced increases in striatal norepinephrine, 3 methoxy-4-hydroxyphenethyleneglycol (MHPG), dopamine, and 5-hydroxyindoleacetic acid (5-HIAA). Following the induction of anesthesia with halothane and oxygen, microdialysis catheters were stereotactically inserted into the striatum of 9 New Zealand white rabbits. Monitored variables included epidural temperature, arterial blood gases and pH, mean arterial pressure, blood glucose concentrations and the electroencephalogram. Following collection of baseline samples of dialysate, animals were randomized to receive a continuous infusion of saline (n = 4) or dexmedetomidine (n = 5). Cerebral ischemia was produced by the inflation of a neck tourniquet and induction of deliberate hypotension. Dialysate collection continued during the ischemic period and for the ensuing 140 min of reperfusion. All dialysate was frozen at -80 degrees C prior to its analysis by liquid chromatography for catecholamine content. There were no significant differences between the two groups for temperature, arterial blood gases, or mean arterial pressure. Blood glucose concentrations increased in the dexmedetomidine group. The electroencephalogram became isoelectric within 30 s of tourniquet inflation in all animals. Analysis of the norepinephrine and MHPG levels revealed significantly lower values for the dexmedetomidine-treated group during and following the ischemic period. There were no differences between groups for extracellular dopamine or 5-HIAA concentrations. These results suggest that the alpha 2 agonist dexmedetomidine can selectively attenuate ischemia-induced increases in striatal norepinephrine concentrations.
authors.affiliation: Department of Anesthesiology, University of California at San Diego, La Jolla 92093.
authors.forename: M
authors.initials: M
authors.lastname: Matsumoto
authors.forename: M H
authors.initials: MH
authors.lastname: Zornow
authors.forename: B C
authors.initials: BC
authors.lastname: Rabin
authors.forename: M
authors.initials: M
authors.lastname: Maze
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000378:metabolism*; D020926:Medetomidine; D017551:Microdialysis; D009638:Norepinephrine / Q000378:metabolism*; D011817:Rabbits
chemical_list: D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D020926:Medetomidine; D009638:Norepinephrine