Ds. Warner et al., SEVOFLURANE AND HALOTHANE REDUCE FOCAL ISCHEMIC BRAIN-DAMAGE IN THE RAT - POSSIBLE INFLUENCE ON THERMOREGULATION, Anesthesiology, 79(5), 1993, pp. 985-992
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.