Etomidate Reduces Ischemia-Induced Glutamate Release in the Hippocampus in Rats Subjected to Incomplete Forebrain Ischemia

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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 centered dot kg-1 centered dot min-1) or thiopental (3 mg centered dot kg-1 centered dot 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. Within the parietal cortex, significant ischemia-induced increases in glutamate and glycine occurred in all three groups. 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. The data suggest that the previously demonstrated ability of etomidate to reduce neuronal injury in the hippocampus may be related to its ability to reduce excitatory neurotransmitter release. A reduction in neuronal injury produced by thiopental probably involves mechanisms other than the modulation of neurotransmitter release. (Anesth Analg 1995;80:933-9)