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Preischemic Administration of Sevoflurane Does not Exert Dose-dependent Effects on the Outcome of Severe Forebrain Ischemia in Rats

Miura, Yoshihide MD, PhD*; Kanazawa, Kaoru DDS, PhD*; Nasu, Ikuko MD, PhD

Journal of Neurosurgical Anesthesiology: July 2015 - Volume 27 - Issue 3 - p 216–221
doi: 10.1097/ANA.0000000000000141
Laboratory Investigation

We previously showed that preischemic administration of high-dose isoflurane worsened the outcome from severe forebrain ischemia in rats. Conversely, high doses of sevoflurane have been reported to improve the outcome from forebrain ischemia when the insult is moderate. To clarify the dose-dependent effects of sevoflurane on severe forebrain ischemia, we performed an outcome study using an identical protocol to that in our previous study with isoflurane. Fasting male Sprague-Dawley rats underwent surgical preparation for forebrain ischemia under halothane anesthesia. Anesthesia was changed to fentanyl/nitrous oxide to eliminate the halothane, after which 30 minutes of 0.5, 1.0, 1.5, 2.0, or 2.5 minimum alveolar concentration sevoflurane was administered. Ten minutes of ischemia was induced by bilateral carotid occlusion plus systemic hypotension, in which cessation of electroencephalographic activity was confirmed. Sevoflurane was discontinued and anesthesia continued with fentanyl/nitrous oxide for an additional 100 minutes. Outcome evaluation at 5 days postischemia included seizure incidence, mortality rate, neuromotor score, and histologic injuries to the cerebral cortex and hippocampal CA1 and CA3. Different doses of sevoflurane did not statistically affect seizure incidence (10.0% to 18.2%), mortality rate (20.0% to 46.7%), cortical damage (mild to moderate degree), or hippocampal CA1 damage (93.7% to 96.7% neuronal necrosis) or CA3 damage (36.3% to 41.7%). Dose-dependent effects of sevoflurane were not observed for any of the outcome variables assessed in this rat model of severe forebrain ischemia.

*Department of Dental Anesthesiology, Health Sciences University of Hokkaido, Hokkaido

Division of Anesthesiology, Okitama Public General Hospital, Yamagata, Japan

The authors have no funding or conflicts of interest to disclose.

Reprints: Yoshihide Miura, MD, PhD, Department of Dental Anesthesiology, Health Sciences University of Hokkaido, Hokkaido 061-0293, Japan (e-mail:

Received May 29, 2014

Accepted October 14, 2014

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