Dexmedetomidine improves neurologic outcome from incomplete ischemia in the rat. Reversal by the alpha 2-adrenergic antagonist atipamezole.
Dexmedetomidine is an alpha 2-adrenergic agonist that decreases central sympathetic activity and reduces the anesthetic requirement for halothane. We evaluated the effect of dexmedetomidine on neurologic and histopathologic outcome from incomplete cerebral ischemia in the rat. Anesthesia was maintained with a 25-micrograms.kg-1.h-1 fentanyl infusion combined with 70% nitrous oxide. Incomplete ischemia was produced by unilateral carotid artery ligation combined with hemorrhagic hypotension to 35 mmHg for 30 min. Arterial blood gas tensions, pH, and head temperature were maintained at normal levels during the experiment. Four ischemic groups were tested: group 1 (n = 15) received an intraperitoneal (ip) saline injection (control); group 2 (n = 10) received an ip injection of 10 micrograms/kg dexmedetomidine 30 min before ischemia; group 3 (n = 10) received 100 micrograms/kg dexmedetomidine; and group 4 (n = 10) received 100 micrograms/kg dexmedetomidine plus 1 mg/kg atipamezole (an alpha 2-adrenergic antagonist). Neurologic outcome was evaluated for 3 days using a graded deficit score. Histopathology was evaluated in coronal section in caudate and hippocampal tissue segments. Dexmedetomidine (10 and 100 micrograms/kg) significantly decreased plasma catecholamines and improved neurologic and histopathologic outcome in a dose-dependent manner compared to control rats (P less than 0.05). Atipamezole abolished the decrease in catecholamines and the improvement in outcome seen with dexmedetomidine, confirming that these effects were mediated by alpha 2-adrenergic receptors. It is concluded that alpha 2-adrenoreceptor stimulation decreases sympathetic activity and decreases ischemic injury in a model of incomplete cerebral ischemia.
Department of Anesthesiology, Michael Reese Hospital, University of Illinois, Chicago 60616.
W E
WE
Hoffman
E
E
Kochs
C
C
Werner
C
C
Thomas
R F
RF
Albrecht
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000097:blood; D007093:Imidazoles / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D008297:Male; D020926:Medetomidine; D009043:Motor Activity / Q000187:drug effects; D009638:Norepinephrine / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D001786:Blood Glucose; D007093:Imidazoles; C050701:atipamezole; D020926:Medetomidine; D009638:Norepinephrine; D004837:Epinephrine