Document Detail


Gamma-aminobutyric acid-mediated neurotransmission in the pontine reticular formation modulates hypnosis, immobility, and breathing during isoflurane anesthesia.
MedLine Citation:
PMID:  19034094     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Many general anesthetics are thought to produce a loss of wakefulness, in part, by enhancing gamma-aminobutyric acid (GABA) neurotransmission. However, GABAergic neurotransmission in the pontine reticular formation promotes wakefulness. This study tested the hypotheses that (1) relative to wakefulness, isoflurane decreases GABA levels in the pontine reticular formation; and (2) pontine reticular formation administration of drugs that increase or decrease GABA levels increases or decreases, respectively, isoflurane induction time.
METHODS: To test hypothesis 1, cats (n = 5) received a craniotomy and permanent electrodes for recording the electroencephalogram and electromyogram. Dialysis samples were collected from the pontine reticular formation during isoflurane anesthesia and wakefulness. GABA levels were quantified using high-performance liquid chromatography. For hypothesis 2, rats (n = 10) were implanted with a guide cannula aimed for the pontine reticular formation. Each rat received microinjections of Ringer's (vehicle control), the GABA uptake inhibitor nipecotic acid, and the GABA synthesis inhibitor 3-mercaptopropionic acid. Rats were then anesthetized with isoflurane, and induction time was quantified as loss of righting reflex. Breathing rate was also measured.
RESULTS: Relative to wakefulness, GABA levels were significantly decreased by isoflurane. Increased power in the electroencephalogram and decreased activity in the electromyogram caused by isoflurane covaried with pontine reticular formation GABA levels. Nipecotic acid and 3-mercaptopropionic acid significantly increased and decreased, respectively, isoflurane induction time. Nipecotic acid also increased breathing rate.
CONCLUSION: Decreasing pontine reticular formation GABA levels comprises one mechanism by which isoflurane causes loss of consciousness, altered cortical excitability, muscular hypotonia, and decreased respiratory rate.
Authors:
Giancarlo Vanini; Christopher J Watson; Ralph Lydic; Helen A Baghdoyan
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anesthesiology     Volume:  109     ISSN:  1528-1175     ISO Abbreviation:  Anesthesiology     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-11-26     Completed Date:  2008-12-24     Revised Date:  2013-06-04    
Medline Journal Info:
Nlm Unique ID:  1300217     Medline TA:  Anesthesiology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  978-88     Citation Subset:  AIM; IM    
Affiliation:
Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan 48109, USA.
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MeSH Terms
Descriptor/Qualifier:
Anesthesia / methods*
Anesthetics, Inhalation / pharmacology
Animals
Cats
Immobility Response, Tonic / drug effects,  physiology*
Isoflurane / pharmacology*
Male
Pons / drug effects,  physiology
Rats
Rats, Sprague-Dawley
Respiration* / drug effects
Reticular Formation / drug effects,  physiology*
Synaptic Transmission / drug effects,  physiology
gamma-Aminobutyric Acid / physiology*
Grant Support
ID/Acronym/Agency:
HL40881/HL/NHLBI NIH HHS; HL57120/HL/NHLBI NIH HHS; HL65272/HL/NHLBI NIH HHS; MH45361/MH/NIMH NIH HHS; R01 HL040881/HL/NHLBI NIH HHS; R01 HL040881-20/HL/NHLBI NIH HHS; R01 HL057120-10/HL/NHLBI NIH HHS; R01 HL065272-08/HL/NHLBI NIH HHS; R37 MH045361-22/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Anesthetics, Inhalation; 26675-46-7/Isoflurane; 56-12-2/gamma-Aminobutyric Acid
Comments/Corrections
Comment In:
Anesthesiology. 2008 Dec;109(6):948-50   [PMID:  19034087 ]

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