Isoflurane improves outcome against cerebral ischemia in the rat. However, the optimal neuroprotective concentration has not been defined. We examined the effects of different isoflurane concentrations on outcome from severe forebrain ischemia in the rat. Fasted rats were subjected to 0.5, 1.0, 1.5, 2.0, or 2.5 minimum alveolar concentration (MAC) isoflurane during 10 min bilateral carotid occlusion plus systemic hypotension. Each isoflurane concentration was administered only before ischemia. Arterial blood pressure was not pharmacologically manipulated. After ischemia, the anesthetic regimen was changed to fentanyl/nitrous oxide and maintained for 2 h. Pericranial temperature was maintained normothermic during the experiment. Neuromotor score, % dead hippocampal CA1 neurons, and cortical injury were measured 5 days postischemia. Preischemic arterial blood pressure decreased as MAC was increased. Animals administered >1.0 MAC frequently exhibited postischemic seizures resulting in increased mortality. There was no difference among MAC conditions for % dead CA1 neurons (93 approximately 95%). In the cortex, neuronal necrosis was less severe with 0.5 MAC and 1.0 MAC isoflurane relative to >1.0 MAC values. The neuromotor score in the 1.0 MAC isoflurane group was superior to the 2.5 MAC group. Dose-dependent effects of preischemic administration of isoflurane on histologic and behavioral outcome after severe forebrain ischemia were observed. Isoflurane MAC values <1.5 provided superior overall outcome relative to larger isoflurane concentrations.

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.

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