| Abstract | 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. |
| Authors | Hiroaki Sakai, Huaxin Sheng, Robert B Yates, Kazuyoshi Ishida, Robert D Pearlstein, David S Warner
(Affiliation: Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA.)
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| Journal | Anesthesiology
(Anesthesiology)
Vol. 106
Issue 1
Pg. 92-9; discussion 8-10
(Jan 2007)
ISSN: 0003-3022 United States |
| PMID | 17197850
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Anesthetics, Inhalation
- Neuroprotective Agents
- Potassium Channels
- mitochondrial K(ATP) channel
- Isoflurane
|
| Topics |
- Anesthetics, Inhalation
(pharmacology)
- Animals
- Blood Pressure
(drug effects)
- Brain Ischemia
(prevention & control)
- Infarction, Middle Cerebral Artery
(drug therapy)
- Isoflurane
(pharmacology)
- Male
- Neuroprotective Agents
(pharmacology)
- Potassium Channels
(physiology)
- Rats
- Rats, Wistar
|
