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ANESTHETIC PHARMACOLOGY

Xenon Does Not Affect -Aminobutyric Acid Type A Receptor Binding in Humans

Elina Salmi, MD^*, Ruut M. Laitio, MD, Sargo Aalto, MSc^*, Anu T. Maksimow, MD^*, Jaakko W. Långsjö, MD^*, Kaike K. Kaisti, MD, Riku Aantaa, MD, Vesa Oikonen, MSc^*, Liisa Metsähonkala, MD^||, Kjell Någren, PhD^*, Esa R. Korpi, MD^¶, and Harry Scheinin, MD^*#;

From the *Turku PET Centre and the #Departments of Pharmacology and Clinical Pharmacology, University of Turku, Turku, Finland; the Department of Psychology, Åbo Akademi University, Turku, Finland; the Department of Anesthesiology and Intensive Care, Turku University Hospital, Turku, Finland, the Department of Otorhinolaryngology – Head and Neck Surgery, Turku University Hospital, Turku, Finland; the ||Department of Child Neurology, Helsinki University Hospital, Helsinki, Finland and the ¶Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki, Finland.

Address correspondence to Elina Salmi, MD, Turku PET Centre, PO Box 52, FIN-20521 Turku, Finland. Address e-mail to anelsa{at}utu.fi.

BACKGROUND: The noble gas xenon acts as an anesthetic with favorable hemodynamic and neuroprotective properties. Based on animal and in vitro data, it is thought to exert its anesthetic effects by inhibiting glutamatergic signaling, but effects on -aminobutyric acid type A (GABA_A) receptors also have been reported. The mechanism of anesthetic action of xenon in the living human brain still remains to be determined.

METHODS: We used the specific GABA_A receptor benzodiazepine-site ligand ¹¹C-flumazenil and positron emission tomography to study the GABAergic effects of xenon in eight healthy male volunteers. Each subject underwent two dynamic 60-min positron emission tomography studies awake and during approximately one minimum alveolar concentration of xenon (65%). Bispectral index was recorded. Cortical and subcortical gray matter regions were analyzed using both automated regions-of-interest analysis and voxel-based analysis.

RESULTS: During anesthesia, the mean ± sd bispectral index was 23 ± 7, and there were no significant changes in heart rate or mean arterial blood pressure. Xenon did not significantly affect ¹¹C-flumazenil binding in any brain region.

CONCLUSIONS: Xenon did not affect ¹¹C-flumazenil binding in the living human brain, indicating that the anesthetic effect of xenon is not mediated via the GABA_A receptor system.

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999