title: Effect of the alpha2-agonist dexmedetomidine on cerebral neurotransmitter concentrations during cerebral ischemia in rats.
abstract: BACKGROUND
  This study investigates whether neuroprotection seen with dexmedetomidine is associated with suppression of peripheral or central sympathetic tone.
  
  
  METHODS
  Thirty fasted male Sprague-Dawley rats were intubated and ventilated with isoflurane and N2O/O2 (fraction of inspired oxygen = 0.33). Catheters were inserted into the right femoral artery and vein and into the right jugular vein. Cerebral blood flow was measured using laser Doppler flowmetry. Bilateral microdialysis probes were placed into the cortex and the dorsal hippocampus. At the end of preparation, the administration of isoflurane was replaced by fentanyl (bolus: 10 microg/kg; infusion: 25 microg x kg(-1) x h(-1)). Animals were randomly assigned to one of the following groups: group 1 (n = 10): control animals; group 2 (n = 10): 100 microg/kg dexmedetomidine administered intraperitoneally 30 min before ischemia; group 3 (n = 10): sham-operated rats. Ischemia (30 min) was produced by unilateral carotid artery occlusion plus hemorrhagic hypotension to a mean arterial blood pressure of 30-35 mmHg to reduce ipsilateral cerebral blood flow by 70%. Pericranial temperature, arterial blood gases, and pH were maintained constant. Cerebral catecholamine and glutamate concentrations and plasma catecholamine concentrations were analyzed using high-performance liquid chromatography.
  
  
  RESULTS
  During ischemia, dexmedetomidine suppressed circulating norepinephrine concentrations by 95% compared with control animals. In contrast, brain norepinephrine and glutamate concentrations were increased irrespective of dexmedetomidine infusion before ischemia.
  
  
  CONCLUSIONS
  The current data show that the increase of circulating catecholamine concentrations during cerebral ischemia was suppressed with dexmedetomidine. In contrast, dexmedetomidine does not suppress elevation in brain norepinephrine and glutamate concentration associated with cerebral ischemia. This suggests that the neuroprotective effects of dexmedetomidine are not related to inhibition of presynaptic norepinephrine or glutamate release in the brain.
authors.affiliation: Klinik für Anaesthesiologie and Institut für klinische Chemie und Pathobiochemie, Technische Universität München, Klinikum rechts der Isar, Munich, Germany. k.engelhard@lrz.tu-muenchen.de
authors.forename: Kristin
authors.initials: K
authors.lastname: Engelhard
authors.forename: Christian
authors.initials: C
authors.lastname: Werner
authors.forename: Susanne
authors.initials: S
authors.lastname: Kaspar
authors.forename: Oliver
authors.initials: O
authors.lastname: Möllenberg
authors.forename: Manfred
authors.initials: M
authors.lastname: Blobner
authors.forename: Monika
authors.initials: M
authors.lastname: Bachl
authors.forename: Eberhard
authors.initials: E
authors.lastname: Kochs
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001784:Blood Gas Analysis; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D002545:Brain Ischemia / Q000378:metabolism*; D002395:Catecholamines / Q000097:blood / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D020927:Dexmedetomidine / Q000494:pharmacology*; D008297:Male; D018377:Neurotransmitter Agents / Q000097:blood / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D001786:Blood Glucose; D002395:Catecholamines; D018377:Neurotransmitter Agents; D020927:Dexmedetomidine