title: Halogenated volatile anesthetics alter brain metabolism as revealed by proton magnetic resonance spectroscopy of mice in vivo.
abstract: Halogenated volatile anesthetics (HVA) are widely used in medicine and research but their effects on brain metabolism in intact organisms are still largely unknown. Here, localized proton magnetic resonance spectroscopy (MRS) of anesthetized mice was applied to evaluate HVA effects on cerebral metabolites in vivo. Experimental protocols combined different concentrations of isoflurane, halothane, sevoflurane, and desflurane with known modulators of adrenergic, GABAergic, and glutamatergic neurotransmission. As a most striking finding, brain lactate increased in individual mice from 1.0 ± 0.6 mM (awake state) to 6.2 ± 1.5 mM (1.75% isoflurane). In addition, relative to total creatine, there were significant isoflurane-induced increases of alanine by 111%, GABA by 20%, choline-containing compounds by 20%, and myo-inositol by 10% which were accompanied by significant decreases of glucose by 51% and phosphocreatine by 9%. The elevation of lactate was most pronounced in the striatum. The HVA effects correlated with the respective minimal alveolar concentrations and were mostly reversible within minutes. The observed alterations are best explained by an HVA-induced stimulation of adrenergic pathways in conjunction with an inhibition of the respiratory chain. Apart from casting new light on cerebral energy metabolism, the present results challenge brain studies of HVA-anesthetized animals.
authors.affiliation: Biomedizinische NMR Forschungs GmbH am Max-PIanck-Institut für biophysikalische Chemie, Göttingen, Germany. susann.boretius@rad.uni-kiel.de
authors.forename: Susann
authors.initials: S
authors.lastname: Boretius
authors.forename: Roland
authors.initials: R
authors.lastname: Tammer
authors.forename: Thomas
authors.initials: T
authors.lastname: Michaelis
authors.forename: Jürgen
authors.initials: J
authors.lastname: Brockmöller
authors.forename: Jens
authors.initials: J
authors.lastname: Frahm
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D006846:Hydrocarbons, Halogenated / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D011522:Protons
chemical_list: D018685:Anesthetics, Inhalation; D006846:Hydrocarbons, Halogenated; D011522:Protons