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Effects of Hypothermia, Pentobarbital, and Isoflurane on Postdepolarization Amino Acid Release during Complete Global Cerebral Ischemia
Authors:Nakashima, Ken MD   Todd, Michael M. MD

Abstract:
Background: Hypothermia and anesthetics may protect the brain during ischemia by blocking the release of excitatory amino acids. The effects of hypothermia (28 degrees C), pentobarbital, and isoflurane on postischemic excitatory amino acid concentrations were compared.

Methods: Rats were anesthetized with 0.8% halothane/50% N2 O, vascular catheters were placed, and a glass microelectrode and microdialysis cannula were inserted into the cerebral cortex. Experimental groups were: (1) control, pericranial, t = 38 degrees C; (2) hypothermia, t = 28 degrees C; (3) pentobarbital, t = 38 degrees Celsius; and (4) isoflurane, t = 38 degrees C. Halothane/N2 O was continued in groups 1 and 2, whereas a deep burst-suppression or isoelectric electroencephalogram was achieved with the test drugs in groups 3 and 4. Cerebral metabolic rates were similar in groups 2, 3, and 4. After a baseline dialysis sample was collected, animals were killed with potassium chloride. The time to terminal depolarization was recorded, after which three consecutive 10-min dialysate samples were collected. Glutamate, aspartate, gamma-aminobutyric acid, and glycine concentrations were measured using high-performance liquid chromatography.

Results: Times to terminal depolarization were shorter in both pentobarbital and isoflurane groups than with hypothermia (103+/- 15 and 127+/-10 vs. 195+/-20 s, respectively, mean +/-SD). However, times to terminal depolarization in all three groups were longer than in control subjects (control = 70+/-9 s). Postdepolarization concentrations of all compounds were lower in hypothermic animals (vs. normothermic control animals), but no reductions in glutamate, aspartate, or glycine concentrations were noted in pentobarbital or isoflurane groups. gamma-aminobutyric acid concentrations were reduced by both anesthetics, but not to the same degree as with hypothermia.

Keywords:
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