Periischemic cerebral blood flow (CBF) does not explain beneficial effectsof isoflurane on outcome from near-complete forebrain ischemia in rats

Background: Isoflurane improves outcome from near-complete forebrain ischem ia in rats compared with fentanyl-nitrous oxide (N2O). Sympathetic ganglion ic blockade with trimethaphan abolishes this beneficial effect. To evaluate whether anesthesia-related differences in cerebral blood flow (CBF) may ex plain these findings, this study compared regional CBF before, during, and after near-complete forebrain ischemia in rats anesthetized with either iso flurane (with and without trimethaphan) or fentanyl-nitrous oxide. Methods: Fasted, normothermic isoflurane anesthetized Sprague-Dawley rats w ere prepared for near-complete forebrain ischemia (10 min of bilateral caro tid occlusion and mean arterial pressure = 30 mmHg). After surgery, rats we re anesthetized with either 1.4% isoflurane (with or without 2.5 mg of trim ethaphan intravenously at onset of Ischemia) or fentanyl-nitrous oxide (25 mu g . kg(-1) . h(-1) . 70% N2O-1). Regional CBF was determined (C-14-iodoa ntipyrine autoradiography) before ischemia, 8 min after onset of ischemia, and 30 min after onset of reperfusion. Results: Regional CBF did not differ significantly among groups at any meas urement interval. Ischemia caused a marked flow reduction to 5% or less of baseline (P < 0.001) in selectively vulnerable regions, such as the cortex, caudoputamen and hippocampus, whereas flow in the brain stem and cerebellu m was preserved. Reperfusion at 30 min was associated with partial restorat ion of flow to 35-50% of baseline values in ischemic structures. Conclusions: The results indicate that improved histologic-behavioral outco me provided by isoflurane anesthesia cannot be explained by differential va sodilative effects of the anesthetic states before, during, or after severe forebrain ischemia. This study also shows severe postischemic delayed hypo perfusion that was not affected by choice of anesthetic or the presence of trimethaphan. Mechanisms other than effects on peri-ischemic CBF must be re sponsible for beneficial effects of isoflurane in this model.