MacIver M B, Mandema J W, Stanski D R, Bland B H
Department of Anesthesia, Stanford University School of Medicine, California 94305-5117, USA.
Anesthesiology. 1996 Jun;84(6):1411-24. doi: 10.1097/00000542-199606000-00018.
Thiopental produces a concentration-dependent continuum of effects on the cortical electroencephalogram (EEG) that has been linked to behavioral measures of anesthetic depth. The complexity of the response, however, limits a clear insight into the neurophysiologic actions of thiopental. The current study investigated thiopental actions on cortical EEG and hippocampal electrical activity, to determine whether similar effects occur on both structures and to compare synchronized activity between these structures.
Thiopental was administered intravenously via an implanted catheter in freely moving rats. Arterial blood oxygen/carbon dioxide concentration, thiopental concentrations, and temperature were monitored and controlled. Neocortical EEG was recorded from implanted dural surface electrodes and hippocampal neuron electrical activity was recorded from stereotaxically placed microelectrodes. Pharmacokinetic models were used to determine effect site concentrations.
Thiopental produced an increase in EEG frequency and amplitude at low concentrations (15-20 micrograms/ml total plasma, approximately 10 microM unbound), which produced a loss of righting reflex. This was followed by a frequency decrease and burst suppression activity at higher concentrations (50-80 micrograms/ml, approximately 60 microM), which produced a loss of tail pinch and corneal reflexes. Higher concentrations of thiopental ( > 60 micrograms/ml) uncoupled synchronized burst discharges recorded in hippocampus and cortex. Isoelectric EEG activity was associated with concentrations of 70-90 micrograms/ml (approximately 80 microM) and a deep level of anesthesia; motor reflexes were abolished, although cardiovascular reflexes remained. In all frequency bands, similar concentration-EEG effect relationships were observed for cortical and hippocampal signals, only differing in the magnitude of response. A reversed progression of effects was observed on recovery.
The results confirm earlier findings in humans and animals and demonstrate that both the hippocampus and neocortex exhibit burst suppression and isoelectric activity during thiopental anesthesia. Thiopental-induced synchronized burst activity was depressed by progressively higher concentrations. The lost synchronization suggests a depression of synaptic coupling between cortical structures contributes to anesthesia.
硫喷妥钠对皮质脑电图（EEG）产生浓度依赖性的连续效应，这与麻醉深度的行为指标相关。然而，该反应的复杂性限制了对硫喷妥钠神经生理作用的清晰洞察。本研究调查了硫喷妥钠对皮质EEG和海马电活动的作用，以确定这两个结构是否出现相似的效应，并比较这些结构之间的同步活动。
通过植入的导管对自由活动的大鼠静脉注射硫喷妥钠。监测并控制动脉血氧/二氧化碳浓度、硫喷妥钠浓度和体温。从植入的硬脑膜表面电极记录新皮质EEG，从立体定位放置的微电极记录海马神经元电活动。使用药代动力学模型确定效应部位浓度。
低浓度（总血浆浓度为15 - 20微克/毫升，游离浓度约为10微摩尔）的硫喷妥钠使EEG频率和振幅增加，导致翻正反射消失。随后，较高浓度（50 - 80微克/毫升，约60微摩尔）时频率降低并出现爆发抑制活动，导致夹尾反射和角膜反射消失。更高浓度的硫喷妥钠（> 60微克/毫升）使海马和皮质中记录到的同步爆发放电解耦。等电位EEG活动与浓度为70 - 90微克/毫升（约80微摩尔）及深度麻醉相关；运动反射消失，尽管心血管反射仍存在。在所有频段，皮质和海马信号观察到相似的浓度 - EEG效应关系，仅反应幅度不同。恢复时观察到效应的逆转过程。
结果证实了先前在人和动物中的发现，并表明在硫喷妥钠麻醉期间海马和新皮质均表现出爆发抑制和等电位活动。硫喷妥钠诱导的同步爆发活动随浓度升高而受到抑制。同步性丧失表明皮质结构之间突触耦合的抑制有助于麻醉。
