Halothane-induced Alterations of Cyclic Nucleotide Concentrations in Three Regions of the Mouse Nervous System

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Abstract
To determine whether halothane alters cyclic nucleotide levels in the nervous system, mice were exposed to air (control) or halothane 0.7, 1.4, 2.4, 3.0 or 4.4% in air, for 15 min. After quick-freezing in liquid N, levels of 3'',5''-cyclic[c)GMP and 3'',5''-cAMP in the cerebral cortex, cerebellum and spinal cord were determined. Lactate and pyruvate were measured in the cerebral cortex and cerebellum as an index of brain oxygenation, and blood-gas, and pH values were measured in replicate experiments. Three groups of studies were made: control, low halothane concentrations (0.7-2.4%) without hypoxia and acidosis and high halothane concentrations (3.0 and 4.4%) accompanied by hypoxia and acidosis. Low halothane cencentrations increased cGMP in the cerebral cortex, depressed it in the cerebellum and had no effect on levels in the spinal cord. Similar alterations were seen after exposure to high halothane concentrations that included a hypoxic component, except that cGMP in the spinal cord was depressed. Since anoxia decreases cGMP in the cerebral cortex and cerebellum, the increase in cGMP in the cortex suggests that the effect of halothane cannot be attributed to hypoxia. The only effect on cAMP was to depress levels of the nucleotide in the cortex at halothane concentrations of 2.4% or more. Halothane apparently has a greater effect on cGMP than on cAMP, and the biochemical responses to the anesthetic may vary among regions of the nervous system.

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