SEVOFLURANE AND HALOTHANE REDUCE FOCAL ISCHEMIC BRAIN-DAMAGE IN THE RAT - POSSIBLE INFLUENCE ON THERMOREGULATION

Background. There has been little systematic examination concerning th e comparative effects of the anesthetized versus the awake state on ou tcome from cerebral ischemia. This experiment evaluated infarct volume and neurologic function in rats subjected to temporary focal ischemia while anesthetized with either sevoflurane or halothane. Outcome in t hese animals was compared to that observed in rats maintained unanesth etized during a similar ischemic insult. Methods: All rats were anesth etized with halothane and surgically prepared for filament occlusion o f the middle cerebral artery. After preparation, one group (Halothane) remained anesthetized with approximately 1.4 MAC halothane. In anothe r group (Sevoflurane), halothane was discontinued and substituted with sevoflurane, which was administered until electroencephalographic bur st suppression was evident (approximately 1.4 MAC). The final group (A wake) was allowed to awaken immediately after the onset of ischemia. M iddle cerebral artery occlusion persisted for 90 min in all groups. Th e middle cerebral artery filament then was removed, and a 96-h surviva l interval was allowed. Neurologic function and infarct volume were de termined. Recent evidence indicates that transient mild hyperthermia o ccurs in awake rats undergoing filament occlusion of the middle cerebr al artery. To examine the potential role of mild hyperthermia in this experiment, a second experiment was performed in which rats anesthetiz ed with halothane underwent 90-min focal ischemia, with pericranial te mperatures held at either 38.0-degrees-C or 39.2-degrees-C. Results: I ntraischemic mean arterial pressure was 20-25 mmHg lower in the two an esthetized groups compared with awake animals. Despite this finding, c ortical infarct volumes (mean +/- SD; Halothane, 1 +/- 32 mm3; Sevoflu rane, 36 +/- 57 MM3 ; Awake, 115 +/- 104 mm3) and subcortical infarct volumes (mean +/- SD; Halothane, 39 +/- 57 MM3; Sevoflurane, 50 +/- 29 mM3 ; Awake, 88 +/- 46 mm3) were reduced in both groups of anesthetiz ed rats. This reduction correlated with improved neurologic function. The rats in whom the pericranial temperature was maintained at 39.2-de grees-C had a larger total infarct volume (218 +/- 81 MM3 ) and increa sed neurologic deficits when compared to those in whom the pericranial temperature was maintained at 38.0-degrees-C (total infarct volume, 7 5 +/- 77 mm3). Conclusions: Both halothane and sevoflurane substantial ly reduced damage in this focal ischemia model when compared to outcom e resulting from the same insult induced in awake rats. The reduction in intraischemic mean arterial pressure caused by the anesthetics did not seem contributory to outcome. Brain temperature differences among the groups were not defined. Because small differences in pericranial temperature were shown to have major effects on outcome, further work is required to determine if differences in brain temperature explain t he observed protective effects of these anesthetics.