Document Detail

Isoflurane provides long-term protection against focal cerebral ischemia in the rat.
MedLine Citation:
PMID:  17197850     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Long-term neuroprotection by isoflurane has been questioned. The authors examined factors in experimental models potentially critical to definition of enduring isoflurane neuroprotection. METHODS: Rats were prepared for temporary middle cerebral artery occlusion (MCAO). Pericranial normothermia was maintained. Neurologic deficits (range, 0-48; 0=no deficit) and cerebral infarct volumes were measured. In experiment 1, rats underwent 50 or 80 min MCAO while awake or anesthetized with 1.8% isoflurane. Blood pressure was controlled with phenylephrine. Outcome was evaluated 2 weeks later. In experiment 2, rats underwent 50 min MCAO while awake or anesthetized with isoflurane, with outcome evaluated 8 weeks later. In experiment 3, rats underwent 50 min MCAO while awake or anesthetized with isoflurane and 2 weeks recovery. Effects of phenylephrine and the mitochondrial adenosine triphosphate-sensitive K channel antagonist 5-hydroxydecanoate were studied. In experiment 4, isoflurane-anesthetized rats underwent 50 min MCAO with permanent or temporary common carotid artery occlusion, with outcome evaluated 2 weeks later. RESULTS: In experiment 1, isoflurane reduced neurologic deficit (median+/-interquartile range; awake vs. isoflurane: 11+/-12 vs. 8+/-6 for 80 min and 13+/-4 vs. 3+/-9 for 50 min; P=0.0006) and infarct size (160+/-97 vs. 84+/-62 mm for 80 min and 169+/-78 vs. 68+/-61 mm for 50 min; P<0.0001). In experiment 2, isoflurane protection persisted at 8 weeks after ischemia. In experiment 3, there was no effect of phenylephrine or 5-hydroxydecanoate. In experiment 4, permanent common carotid ligation increased infarct size threefold versus temporary occlusion. CONCLUSIONS: Isoflurane repeatedly improved long-term neurologic and histologic outcome from focal ischemia independent of ischemia duration, perfusion pressure, or pretreatment with 5-hydroxydecanoate.
Hiroaki Sakai; Huaxin Sheng; Robert B Yates; Kazuyoshi Ishida; Robert D Pearlstein; David S Warner
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anesthesiology     Volume:  106     ISSN:  0003-3022     ISO Abbreviation:  Anesthesiology     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2007-01-01     Completed Date:  2007-02-20     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  1300217     Medline TA:  Anesthesiology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  92-9; discussion 8-10     Citation Subset:  AIM; IM    
Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA.
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MeSH Terms
Anesthetics, Inhalation / pharmacology*
Blood Pressure / drug effects
Brain Ischemia / prevention & control*
Infarction, Middle Cerebral Artery / drug therapy
Isoflurane / pharmacology*
Neuroprotective Agents / pharmacology*
Potassium Channels / physiology
Rats, Wistar
Grant Support
Reg. No./Substance:
0/Anesthetics, Inhalation; 0/Neuroprotective Agents; 0/Potassium Channels; 0/mitochondrial K(ATP) channel; 26675-46-7/Isoflurane

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