Neuroprotection by the alpha 2-adrenoreceptor agonist dexmedetomidine in a focal model of cerebral ischemia.
BACKGROUND
Dexmedetomidine, a highly selective alpha 2-adrenoreceptor agonist, decreases central sympathetic activity and reduces the anesthetic requirement of halothane. Preliminary studies show that dexmedetomidine improves the outcome from ischemic injury and, therefore, may have potential therapeutic value.


METHODS
The authors studied 14 rabbits that underwent a 2-h occlusion of the left internal carotid, anterior cerebral, and middle cerebral arteries, followed by 4 h of reperfusion. Ten minutes after occlusion, the animals were treated with either normal saline (n = 7) or dexmedetomidine (n = 7) using a computer-controlled infusion rate calculated to maintain a steady state plasma concentration. Halothane concentration was reduced by 50% for dexmedetomidine-treated animals to maintain a comparable level of anesthesia. Somatosensory evoked potentials were used to confirm adequate ischemia, and injury was assessed by histopathology.


RESULTS
There were significant differences in the area of ischemic neuronal damage between the groups in the cortex (halothane alone, 38.2 +/- 6.0% SEM vs. halothane plus dexmedetomidine, 20.0 +/- 2.7% SEM, P = 0.018), but not in the striatum (halothane alone, 68.7 +/- 12.6% SEM vs. halothane plus dexmedetomidine, 43.5 +/- 15.9% SEM, P = 0.24), nor in physiologic parameters. Dexmedetomidine plasma levels obtained every 90 min showed a mean of 4.0 +/- 0.15 ng/ml.


CONCLUSIONS
Results from this study indicate that postischemic administration of dexmedetomidine, in a dose that reduces the anesthetic requirements by 50%, has a neuroprotective effect in this model of focal cerebral ischemia.
Maier
C
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Department of Neurosurgery, Stanford University Medical Center, California 94305.
Steinberg
G K
GK
Sun
G H
GH
Zhi
G T
GT
Maze
M
M
D000316:Adrenergic alpha-Agonists / Q000627:therapeutic use*; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D020926:Medetomidine; D008955:Models, Cardiovascular; D011817:Rabbits
D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D020926:Medetomidine