Anesthetic effects on cerebral metabolic rate predict histologic outcome from near-complete forebrain ischemia in the rat

Background: Although reduction of cerebral metabolic rate is thought to con tribute to anesthetic neuroprotection, histologic evidence to support this concept has not been provided. In this study, histologic outcome was evalua ted in rats subjected to different durations of severe forebrain ischemia w hile anesthetized with volatile anesthetics that have substantially differe nt effects on cerebral metabolic rate. Methods: Normothermic rats that underwent fasting were anesthetized with 0. 75 minimum alveolar concentration (MAC) isoflurane-60% nitrous oxide (N2O) or 0.75 MAC halothane-60% N2O, Ischemia was induced with use of a combinati on of bilateral carotid occlusion and controlled hypotension, Rats in the i soflurane group were subjected to 6.5 min or 8.0 min ischemia, whereas the halothane group received 6.5 min ischemia. Histologic damage was assessed 4 days later. Results: With 6.5 min ischemia, mean +/- SD, hippocampal CA1 percent of dea d (% dead) neurons was reduced with isoflurane-N2O (45 +/- 18) versus halot hane-N2O (60 +/- 23,P = 0.023). Eight minutes of ischemia increased % dead neurons in the isoflurane-N2O group (60 +/- 17, P = 0.017), There was no di fference between the isoflurane 8.0-min and halothane 6.5-min groups (P = 0 .935). A similar pattern was observed in hippocampal CA4 and the neocortex, Striatal damage was not affected by anesthetic or ischemic duration. Conclusions: At 6.5 min ischemia, isoflurane provided improved outcome vers us halothane. Previous research has shown that 0.75 MAC isoflurane-N2O incr eases the time to onset of ischemic depolarization by 1.5 min and reduces c erebral metabolic rate by 42% versus 0.75 MAC halothane-N2O. In the current study, when the duration of ischemia was increased by 1.5 min in the isofl urane-N2O group, histologic outcome became similar to that in halothane-N2O -anesthetized rats. These results provide evidence that cerebral metabolic rate reduction has an advantageous effect on outcome from severe brain isch emia, but also suggest that such benefit is likely to be small.