title: Etomidate reduces ischemia-induced glutamate release in the hippocampus in rats subjected to incomplete forebrain ischemia.
abstract: Etomidate and thiopental reduce ischemic neuronal injury but the mechanism by which they do so is not clear. Ischemia-induced release of the excitatory neurotransmitters glutamate and glycine is thought to play a major role in the pathophysiology of ischemic injury. To determine how etomidate and thiopental modulate excitatory transmitter release, their effect on the release of glycine and glutamate during ischemia was evaluated by microdialysis in the hippocampus and cortex of rats. Three groups of Wistar-Kyoto rats (n = 5/group) were studied. In the etomidate and thiopental groups, electroencephalogram (EEG) burst-suppression was achieved and maintained by a continuous infusion of either etomidate (0.6 mg.kg-1.min-1) or thiopental (3 mg.kg-1.min-1) 40 min prior to ischemia. Halothane anesthetized (1 minimum alveolar anesthetic concentration [MAC]) rats served as controls. Ischemia was induced in all three groups by bilateral carotid artery occlusion with simultaneous hypotension to 35 mm Hg for 10 min. Pericranial temperature was controlled at 38 degrees C. Dialysate was collected before, during, and after ischemia. The levels of glutamate and glycine in the dialysate were measured by high-performance liquid chromatography. Within the hippocampus, both glutamate and glycine levels increased significantly in the thiopental and control groups. By contrast, in the etomidate group, glutamate and glycine levels did not increase during ischemia, and peak levels were significantly less than those in the thiopental group. Peak glutamate levels in the thiopental group were significantly larger than in the control group, whereas the peak glycine levels were not different among the groups.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Anesthesiology, University of California, San Diego, USA.
authors.forename: P M
authors.initials: PM
authors.lastname: Patel
authors.forename: R L
authors.initials: RL
authors.lastname: Goskowicz
authors.forename: J C
authors.initials: JC
authors.lastname: Drummond
authors.forename: D J
authors.initials: DJ
authors.lastname: Cole
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology*; D002851:Chromatography, High Pressure Liquid; D005045:Etomidate / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D005998:Glycine / Q000378:metabolism; D006624:Hippocampus / Q000098:blood supply / Q000378:metabolism*; D010296:Parietal Lobe / Q000098:blood supply / Q000378:metabolism; D016548:Prosencephalon / Q000098:blood supply; D051381:Rats; D011921:Rats, Inbred WKY; D013874:Thiopental / Q000494:pharmacology
chemical_list: D018698:Glutamic Acid; D013874:Thiopental; D005998:Glycine; D005045:Etomidate