在局灶性脑缺血大鼠模型中，引发戊巴比妥的最大神经保护作用并不需要脑电图爆发抑制。

Electroencephalographic burst suppression is not required to elicit maximal neuroprotection from pentobarbital in a rat model of focal cerebral ischemia.

作者信息

Warner D S, Takaoka S, Wu B, Ludwig P S, Pearlstein R D, Brinkhous A D, Dexter F

机构信息

Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710, USA.

出版信息

Anesthesiology. 1996 Jun;84(6):1475-84. doi: 10.1097/00000542-199606000-00024.

DOI:10.1097/00000542-199606000-00024

PMID:8669689

Abstract

BACKGROUND

Barbiturates have previously been demonstrated to reduce focal cerebral ischemic brain damage. However, the dose of drug required to elicit maximal neuroprotection has not been defined. The authors' hypothesized that doses of pentobarbital substantially lower than those required to cause electroencephalographic burst suppression would result in maximal magnitudes of reduction of cerebral infarct volume.

METHODS

Wistar rats underwent 90 min of filament occlusion of the middle cerebral artery while either awake (control), or anesthetized with intravenous sodium pentobarbital administered to preserve an active electroencephalogram (15-23 mg.kg-1.h-1) or a pattern of burst suppression (45-60 mg.kg-1.h-1; n = 17). During ischemia and for the first 6 h of recirculation, brain temperature was rigorously controlled at 38.0 +/- 0.2 degrees C. Rats were allowed a recovery interval of 7 days after which neurologic function and cerebral infarct volume were assessed. In nonischemic rats undergoing a similar anesthetic protocol, the cerebral metabolic rate of glucose utilization was measured at each anesthetic depth.

RESULTS

Relevant physiologic values were similar between groups. Total infarct volume (mean +/- SD) was smaller in the active electroencephalogram group than in the control group (124 +/- 68 mm3 versus 163 +/- 66 mm3; P < 0.05). Increasing the dose of pentobarbital (burst suppression) did not further decrease infarct volume (128 +/- 54 mm3). Neurologic score and infarct volume were positively correlated (P < 0.001). Cerebral metabolic rate of glucose utilization was reduced by 56% in the burst suppression group versus 43% in the active electroencephalogram pentobarbital group (P < 0.001).

CONCLUSIONS

Sodium pentobarbital administered at either dose (active electroencephalogram or burst suppression) resulted in an approximately equal to 25% reduction of cerebral infarct size, indicating that burst suppression is not required to elicit maximal neuroprotective efficacy.

摘要

背景

先前已证明巴比妥类药物可减轻局灶性脑缺血性脑损伤。然而，引发最大神经保护作用所需的药物剂量尚未确定。作者推测，戊巴比妥的剂量大幅低于引起脑电图爆发抑制所需的剂量，将导致脑梗死体积减少的最大幅度。

方法

Wistar大鼠在清醒（对照组）或静脉注射戊巴比妥钠麻醉以维持活跃脑电图（15 - 23毫克·千克⁻¹·小时⁻¹）或爆发抑制模式（45 - 60毫克·千克⁻¹·小时⁻¹；n = 17）的情况下，进行90分钟的大脑中动脉线栓阻塞。在缺血期间和再灌注的前6小时，脑温严格控制在38.0±0.2℃。大鼠给予7天的恢复间隔，之后评估神经功能和脑梗死体积。在接受类似麻醉方案的非缺血大鼠中，在每个麻醉深度测量葡萄糖利用的脑代谢率。

结果

各组间相关生理值相似。活跃脑电图组的总梗死体积（平均值±标准差）小于对照组（124±68立方毫米对163±66立方毫米；P < 0.05）。增加戊巴比妥剂量（爆发抑制）并未进一步减少梗死体积（128±54立方毫米）。神经评分与梗死体积呈正相关（P < 0.001）。爆发抑制组葡萄糖利用的脑代谢率降低了56%，而活跃脑电图戊巴比妥组降低了43%（P < 0.001）。