Distinct arousal states are induced by monoaminergic and cholinergic stimulation during isoflurane general anesthesia
Sunday, Nov 14, 2010, 9:00 AM -10:00 AM
, J. F. COTTEN
, A. CIMENSER
, E. N. BROWN
Anesthesia, Critical Care and Pain Med., Massachusetts Gen. Hosp., Boston, MA;
Anaesthesia, Harvard Med. Sch., Boston, MA;
Brain and Cognitive Sci., MIT, Cambridge, MA;
Harvard - MIT Div. of Hlth. Sci. and Technol., Boston, MA
Accumulating evidence suggests that ascending arousal pathways promote emergence from general anesthesia (GA). Elucidating these mechanisms may lead to improved pharmacological control over the arousal states of anesthetized patients, better neurophysiological monitors to detect intraoperative awareness, and ultimately a safer and more efficient practice of anesthesiology. The objective of this study was to assess the potential roles of a monoamine transporter inhibitor (methylphenidate, MPH) and a cholinesterase inhibitor (physostigmine, PHY) in promoting emergence from GA.
At least 1 week after implantation of surface EEG electrodes, a 24-gauge intravenous (IV) catheter was placed in a rat's lateral tail vein under GA with isoflurane (ISO). The animal was then placed supine in an anesthetizing chamber equipped with a port to administer IV medications. Group 1 animals received ISO at a dose sufficient to maintain loss of righting reflex, and group 2 animals received ISO at a dose that maintained a burst suppression ratio (BSR) between 60-80%. After reaching a steady state dose of ISO, MPH (5 mg/kg IV) or PHY (0.2 mg/kg IV) was administered.
Group 1 rats that received MPH promptly exhibited signs of arousal (i.e. spontaneous movement, head up, eyes open) and had restoration of the righting reflex within 5 minutes. EEG spectral analysis demonstrated a shift in power from the delta band (<4 Hz) to the theta band (4-8 Hz) after administration of MPH. In contrast, the righting reflex was not restored in rats that received PHY. Group 2 rats that received PHY had >50% reduction in BSR, but animals that received MPH exhibited no change.
MPH produces behavioral evidence of arousal during continuous exposure to low-dose ISO (Group 1), although it fails to decrease BSR during high-dose exposure (Group 2). Conversely, PHY reduces BSR during exposure to high doses of ISO, but fails to restore the righting reflex at low-dose ISO. These results suggest that stimulation of monoaminergic and cholinergic systems produces distinct arousal states during GA.
Dept. of Anesthesia, Massachusetts General Hospital
[Authors]. [Abstract Title]. Program No. XXX.XX. 2010 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2010. Online.
2010 Copyright by the Society for Neuroscience all rights reserved. Permission to republish any abstract or part of any abstract in any form must be obtained in writing by SfN office prior to publication.
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