异氟醚预处理通过激活蛋白激酶C-δ诱发心肌纤维膜ATP敏感性钾通道持久敏感化

背景：吸入麻醉药预处理的心肌保护作用机制涉及到心肌纤维膜A胛敏感性钾通道（sarcKATP）的激活，本实验通过研究短暂麻醉药预处理是否能产生持久sarcKATP敏感化，及其是否是通过蛋白激酶C（PKC）介导，进而研究麻醉药预处理的记忆时相。     

吸入麻醉下内隐记忆与脑电双频谱指数的关系

目的 研究相同ＭＡＣ水平的吸入麻醉药对内隐记忆的影响,分析内隐记忆消失的界值。方法 ５４例行择期腹部手术患者,随机分为异氟醚、七氟醚、地氟醚３组（每组１８例）,麻醉采用吸入麻醉复合硬膜外麻醉,每组又依吸入麻醉浓度不同分成３个亚组（每组６例）,吸入麻醉药呼末ＭＡＣ值分别为０．４、０．５、０．６,监测患者入室后、麻醉后、切皮后、术中的双频谱指数（ＢＩＳ）,９５％的谱边缘频率（ＳＥＦ）,调查患者术后８ｈ     

七氟醚 异氟醚和安氟醚对离体兔胸主动脉环收缩功能的影响

目的：比较吸入麻醉药七氟醚、异氟醚和安氟醚对离体兔胸主动清脉环收缩功能的影响。方法：将取自２４只新西兰白兔的离体胸主动脉环随机分为七氟醚、异氟醚、安氟醚三组。衔用ＰＥ产生主动张力,稳定后分别吹入上述三种吸入麻醉药七氟醚记录不同浓度时的血管张力。结果：与基础值（麻醉药浓度为零时）相比,血管张力在三种吸入麻醉药２为１．０、１．５、２．０ＭＡＣ时均降低（Ｐ值分别小于０．０５、０．０５、０．０１）。安氟醚     

吸入麻醉药促发育期神经元凋亡的分子机制

背景 长期以来,人们一直认为吸入麻醉药的麻醉作用是可逆的,对中枢神经系统不会遗留任何副作用.近年基础研究发现,实验动物尤其是处于发育期动物,暴露于吸入麻醉药后,可出现记忆、认知功能障碍.这种现象的产生可能与吸入麻醉药导致的神经元凋亡增加有关.目的 综述吸入麻醉药诱导发育期大脑神经元凋亡可能的分子机制.内容 吸入麻醉药可能通过影响神经递质及受体、信号转导通路,并可引起氧化应激反应、β-淀粉样蛋白质集聚,从而导致神经细胞凋亡.趋向 对吸入麻醉药神经毒性防治的研究起推动作用.     

不同静脉和吸入麻醉药对罗库溴铵肌肉松弛作用的影响

目的：研究不同静脉和吸入麻醉药对罗库溴铵肌肉松弛作用的影响。方法：５０例病人分为５组，观察并比较了静脉麻醉药咪唑安定、异丙酚和吸入麻醉药（１．２ＭＡＣ）安氟醚、异氟醚和七氟醚对罗库溴铵肌肉松弛作用的影响，以及罗库溴铵对血流动力学的影响。结果：肌松作用起效时间５组间无显著差异，平均为４４．５～４９．１秒。其临床维持时间、７５％恢复时间和恢复指数三种吸入麻醉药组均显著长于两种静脉麻醉药组（Ｐ＜０．０１），而三种吸入麻醉药组间和两种静脉麻醉药组间则无显著差异。咪唑安定组和异丙酚组的肌松作用临床维持时间平均为３６．２～４１．５分钟。罗库溴铵静脉给药后血压、心率维持平稳。结论：罗库溴铵具有起效快、中等作用维持时间和血流动力学稳定的特点，但与高浓度吸入麻醉药合用可使其作用时间明显延长。     

吸入麻醉药的神经毒性作用及其产生机制

背景 吸入麻醉药具有安全、有效的特点,已广泛应用于各种手术的临床麻醉.大量实验研究表明,常用的吸入麻醉药均有不同程度的神经毒性作用,尤其是对于发育高峰期的大脑. 目的 探讨吸入麻醉药对幼年动物及小儿的神经毒性作用及其可能机制. 内容 吸入麻醉药具有神经毒性,可能会引起幼年动物学习及记忆功能的损伤,影响小儿神经发育导致认知行为障碍.目前认为其机制可能是多途径的,包括受体的影响、突触可塑性变化、脑的炎性反应和相关脑内物质的改变等. 趋向 正确了解吸入麻醉药的神经毒性作用不仅对婴幼儿麻醉药物的选择具有非常重要的指导意义,并且通过探索机制寻找可能的处理方法,为今后的临床处理提供新的思路.     

挥发性吸入麻醉药对短潜伏期体感诱发电位的影响

目的 选择合适的吸入麻醉药及其浓度，为术中体感诱发电位（SSEP）监测提供参考。方法 60例择期行神经外科手术的患者随机分为三组：安氟醚组、怫氟醚组和地氟醚组。每个患者在清醒和挥发性麻醉药呼气末浓度分别为0．3、0．5、0．75、1．0和1．5MAC时记录正中神经体感诱发电位N13（颈髓）及N20（大脑皮层）。观察皮层电位N20、颈髓电位N13的潜伏期、波幅和中枢传导时间（CCT）的变化。结果 三种吸入麻醉药不改变皮层下电位N13的潜伏期和波幅（P＞0．05）。而皮层电位N20的潜伏期和中枢传导时间（CCT）随安氟醚、异氟醚和地氟醚呼气末浓度的增加，逐渐延长，波幅则下降（P＜0．05）。其中吸入安氟醚在呼出末浓度1．0MAC时有3例患者波形消失，在1．5MAC时共有6例患者波形消失，而异醚和地氟醚呼吸末浓度只在1．5MAC时有3个患者波形消失。结论（1）挥发性吸入麻醉药对SSEP的皮层成分N20波潜伏期和波幅的影响呈浓度依赖性，对皮层下成分N13波影响轻微；（2）在三种吸入麻醉药中，安氟醚对皮层SSEP影响比异氟醚及地氟醚更大，而后者作用相似。术中SSEP监测时，安氟醚在呼气末浓度不大于0．75MAC时是合适的；异氟醚、地氟醚在呼气末浓度不大于1．0MAC时是合适的。     

关于机体对吸入麻醉药反应的起源和进化假说

本文从进化的观点阐述了机体为何对吸入麻醉药产生反应。有猜想认为：现在机体对吸入麻醉药的反应性源自离子通道对吸入麻醉药的敏感性，并且自共同的祖先单细胞机体即存在的麻醉药敏感离子通道传承而来（比如，对麻醉药的反应并不是神经系统的适应，而是多细胞起源之前就存在离子通道的适应）。这种敏感性可能因多细胞机体突触持续的自然选择而得到提高。 特别提出如下几点假想：1）单细胞机体的一个有益特性是离子通道对存在于环境中影响其构象平衡的化合物的协调反应；2）这种协调反应预防正离子进入细胞后的有害后果，从而增加机体的适应性；3）这些化合物（可能包括阳离子、阴离子、两性离子和不带电化合物）模仿具有接触活性的吸入麻醉药，并通过改变与通道功能相匹配的双分子层特性来调节离子通道功能。此假说与吸入麻醉药的已知特性相一致。除此之外，此假说还引出了非挥发性化合物在离子通道和动物体具有类似麻醉的调节功能的试验性预见，这些化合物包括在健康和疾病状态调节离子通道功能的内源性化合物。后者包括在某些终末期脏器衰竭和遗传性代谢性疾病中产生增加的代谢产物。有些预见已经被试验证实是正确的。     

肥胖轻度影响人类吸入麻醉药的药物动力学

背景很少有研究确定肥胖对吸入麻醉药药物动力学的影响。我们假设肥胖患者体重指数（BMI）的增加与强效吸入麻醉药在脂肪中的溶解度之间的相互影响,可能增加麻醉药的摄取量和减慢麻醉药输出浓度（FD）和吸入浓度（FI）达到稳态肺泡内的浓度（FA或潮气量末浓度）的速率该假设提示肥胖对于易溶性麻醉药的影响更大（如异氟烷和地氟烷比较）。方法107例患者,ASA分级Ⅰ～Ⅲ级,应用丙泊酚诱导,注射肌肉松弛刺行气管插管,直用50％氧化亚氮行控制通气,呼气未二氧化碳维持在35—45mmHg之间．以1L／min的流量给予异氧皖或地氧烷,使其FD浓度足以维持FA在0．6MAC（兮别为0．7％或3．7％）,分别于开始吸入麻醉药后5、10、20、40、60、90、120、150和180分钟时测定FD、FI及FA。结果59例患者接受异氟烷,48例患者接受地氟烷。体重指数在18～63kg／m^2之间,各麻醉组之间人口统计学变量无差异。对异氟烷而言,FD／FA或FI／FA在18个时间点中有9个与体重指数（BMI）轻微（但显著）相关,而对于地氟烷来说,FD／FA或FI／FA仅有一个时间点与体重指数（BMI）明显相关（P〈0.01）。将每组分为非肥胖患者（BMI〈30）和肥胖患者（BMI〉／30）后,应用异氟烷时肥胖患者的FD／FA或FI／FA在4个时间点较高,而非肥胖细和应用地氟烷者之间无差异。接受异氟烷的患者麻醉停药后对指令的反应时间较长,而肥胖者异氟烷和地氟烷的唤醒时间均未延长或缩短、运用BMI来标准化FI／FA和FD／FA后,异氟烷的中位数均高于地氟烷的中位数3到5倍,在血／气分配系数（3．1）、肌肉／气分配系数（4．6）、脂肪／气配配系数（5．4）的比值上具有可比性。结论BMI轻度影响FI／FA和FD／FA,麻醉药在所有组织中溶解度较大时该效应最为显著。BMI增加会增强麻醉药摄取从而增大维持肺泡内麻醉药浓度稳态时麻醉药的需要量,尤其是应用易溶性麻醉药时。但是,随着体重增加而增加的量并不大。     

不同浓度七氟醚可双向调节大鼠学习记忆及海马ARC蛋白表达

背景：术中知晓和术后认知功能障碍是困扰麻醉医师的棘手问题。以往多认为与全身麻醉药物对神经系统的影响有关。但近来不断有实验研究证实．低浓度吸入麻醉气体在特定环境下反而会兴奋大脑功能．甚至产生脑保护的作用。显然全麻药物对大脑认知功能的影响机制仍未明瞭。全身麻醉药物七氟醚已广泛应用于各类临床手术．其对哺乳类动物中枢神经系统是否及如何产生影响是我们一直在探讨的课题。细胞骨架蛋白ARC可在大脑海马结构大量表达．已证实可依据其表达情况来考察神经元的活性．以及突触可塑性的变化。目前认为其表达程度可作为检测学习记忆形成的指标。近来有学者发现，较低浓度的七氟醚可引发中枢神经兴奋现象．并猜测亚麻醉剂量对于中枢神经系统具潜在保护作用。为进一步证实这一现象．本研究拟结合ARC蛋白和抑制性逃避（inhibitory avoidance．IA）这一行为学实验来进行深入探讨。方法：250－300g雄性SD大鼠随机分为3组：空白组，极低浓度七氟醚吸入组（0．11％SEV）和低浓度七氟醚吸入组（0．3％SEV）。依据分组依次将大鼠安置于连接有低流量（0．5L／min）闭合环路吸入麻醉系统的特制容器内，分别给予吸入空气，0．11％SEV（0．05MAC）和0．3％SEV（0．14MAC）各45min。结束后马上进行单次IA训练（0．4mA,2s），24小时后进行IA记忆（潜伏期）检测。另取一批大鼠在IA初次训练后45min处死取材．以western-blotting方法检测脑内海马ARC蛋白的表达水平．以real—timePCR方法检测ARC的mRNA转录水平。结果：与吸入空气组相比。0．11％sEV组的24小时IA记忆潜伏期明显延长，而0．3％SEV组的24小时IA记忆潜伏期缩短：相应地．0．1196SEV组的海马ARC蛋白表达增加．而0．30％SEV组ARC蛋白的表达减少。但ARC的mRNA水平却始终无显著差异。结论：吸入不同浓度的七氟醚能对大鼠的学习记忆能力产生双相作用．这种现象伴有海马蛋白ARC表达的相应改变．却没有相应mRNA水平的改变。提示全麻药物七氟醚对于记忆的双向调节存在即可早期基因如NARC对神经元突触可塑性的作用．但这种干预可能体现在转录后水平。     

长时程增强及长时程抑制与全麻药关系的研究进展

长时程增强(long-term potentation,LTP)和长时程抑制(long-term depression,LTD)作为突触可塑性的两种不同表达方式,是学习记忆活动的细胞水平的生物学基础,与记忆的形成和维持有关.近年来许多研究表明,全身麻醉药的遗忘、镇静催眠及镇痛等效应与影响神经系统的突触可塑性即LTP和LTD有密切的关系.现就近年来LTP及LTD与全身麻醉药之间的最新进展作一综述.     

Isoflurane antagonizes the capacity of flurothyl or 1,2-dichlorohexafluorocyclobutane to impair fear conditioning to context and tone

In animals, the conventional inhaled anesthetic, isoflurane, impairs learning fear to context and fear to tone, doing so at concentrations that produce amnesia in humans. Nonimmobilizers are inhaled compounds that do not produce immobility in response to noxious stimulation, nor do they decrease the requirement for conventional inhaled anesthetics. Like isoflurane, the nonimmobilizer 1,2-dichlorohexafluorocyclobutane (2N) impairs learning at concentrations less than those predicted from its lipophilicity to produce anesthesia. The capacity of the nonimmobilizer di-(2,2,2,-trifluoroethyl) ether (flurothyl) to affect learning and memory has not been studied. Both nonimmobilizers can cause convulsions. We hypothesized that if isoflurane, 2N, and flurothyl act by the same mechanism to impair learning and memory, their effects should be additive. We found that isoflurane, 2N, and flurothyl (each, alone) impaired learning fear to context and fear to tone in rats, with the nonimmobilizers doing so at concentrations less than those that cause convulsions. (Fear was defined by freezing [volitional immobility] in the presence of the conditioned stimulus [context or tone].) However, the combination of isoflurane and 2N or flurothyl produced an antagonistic rather than an additive effect on learning, a finding in conflict with our hypothesis. And flurothyl was no less potent than 2N (at least no less potent relative to the concentration of each that produced convulsions) in its capacity to impair learning. We conclude that conventional inhaled anesthetics and nonimmobilizers impair learning and memory by different mechanisms. The basis for this impairment remains unknown. IMPLICATIONS: Conventional inhaled anesthetics and nonimmobilizers are antagonistic in their effects on learning and memory, and this finding suggests that they impair learning and memory, at least in part, by different mechanisms.     

麻醉常用药物对异氟醚作用的影响

异氟醚是全世界使用最多的吸入麻醉药,其作用机制有许多学说,但具体的作用机制还是不明确.传统的MAC主要作用在脊髓;而其镇静、催眠等作用主要在大脑.异氟醚常与许多其他药物联合应用.阿片类药物、局麻药、苯二氮革类药物、a2受体激动剂以及其他吸入麻醉药等都能影响其催眠,麻醉和镇痛作用和其抑制记忆、反应和学习的能力.     

全麻药物对脑神经毒作用的研究进展

从细胞培养、啮齿类动物和非人类灵长类动物的实验研究中得到越来越多的证据:临床常用全麻药物对各期脑神经细胞产生毒性作用,损伤中枢神经系统,特别对处于发育高峰期的大脑影响更大,并影响以后的学习记忆功能.现综述这些事实及目前全麻药物神经毒性作用的机制假设,目的 是让人们对全麻药物毒性作用的最新研究进展有一了解,转变临床麻醉的一些观念.     

Memory enhancing effect of low-dose sevoflurane does not occur in basolateral amygdala-lesioned rats

BACKGROUND: Certain anesthetics might enhance aversive memory at doses around 0.1 minimum alveolar concentration. This issue was investigated in a rat model of learning and memory. In addition, evidence for basolateral amygdala (BLA) involvement in mediating memory enhancement was sought. METHODS: First, the memory-enhancing potential of various anesthetics was determined. Rats underwent single-trial inhibitory avoidance training (0.3 mA shock/1 s) during exposure to air, 0.11% sevoflurane, 0.10% halothane, 0.77% desflurane, or 0.12% isoflurane. Memory was assessed at 24 h. Second, the BLA contribution to sevoflurane memory enhancement was determined. Rats received bilateral excitotoxic N-methyl-D-aspartate (12.5 mg in 0.2 microl per BLA) lesions of the BLA 1 week before training. Memory of lesioned and control rats was compared 24 h after training in air or sevoflurane. RESULTS: Sevoflurane exposure during training significantly enhanced 24-h retention performance for both nonoperated and sham-operated rats (P < 0.005 for both vs. their respective controls). Halothane, but not desflurane or isoflurane, also enhanced retention performance (P < 0.05). However, halothane-induced hyperalgesia during learning clouds interpreting enhanced retention performance solely as a memory consolidation effect. BLA lesions significantly reduced and equalized retention performance for both sevoflurane- and air-exposed animals. Lesions blocked memory enhancement without also causing a generalized inability to learn, because additional training revealed essentially normal task acquisition and 24-h memory. CONCLUSIONS: Sevoflurane enhances aversive memory formation in the rat. The BLA likely contributes to this effect. The risk of aversive memory formation may be enhanced during exposure to low-dose sevoflurane.     

Memory Enhancing Effect of Low-dose Sevoflurane Does Not Occur in Basolateral Amygdala-lesioned Rats

Background: Certain anesthetics might enhance aversive memory at doses around 0.1 minimum alveolar concentration. This issue was investigated in a rat model of learning and memory. In addition, evidence for basolateral amygdala (BLA) involvement in mediating memory enhancement was sought.

Methods: First, the memory-enhancing potential of various anesthetics was determined. Rats underwent single-trial inhibitory avoidance training (0.3 mA shock/1 s) during exposure to air, 0.11% sevoflurane, 0.10% halothane, 0.77% desflurane, or 0.12% isoflurane. Memory was assessed at 24 h. Second, the BLA contribution to sevoflurane memory enhancement was determined. Rats received bilateral excitotoxic N-methyl-d-aspartate (12.5 mg in 0.2 [mu]l per BLA) lesions of the BLA 1 week before training. Memory of lesioned and control rats was compared 24 h after training in air or sevoflurane.

Results: Sevoflurane exposure during training significantly enhanced 24-h retention performance for both nonoperated and sham-operated rats (P < 0.005 for both vs. their respective controls). Halothane, but not desflurane or isoflurane, also enhanced retention performance (P < 0.05). However, halothane-induced hyperalgesia during learning clouds interpreting enhanced retention performance solely as a memory consolidation effect. BLA lesions significantly reduced and equalized retention performance for both sevoflurane- and air-exposed animals. Lesions blocked memory enhancement without also causing a generalized inability to learn, because additional training revealed essentially normal task acquisition and 24-h memory.     

Nonhalogenated anesthetic alkanes and perhalogenated nonimmobilizing alkanes inhibit alpha(4)beta(2) neuronal nicotinic acetylcholine receptors

The nonhalogenated anesthetic alkanes, cyclopropane and butane, do not enhance gamma-aminobutyric acid-elicited GABAergic currents, suggesting that these agents produce anesthesia via interactions with other molecular targets. Perhalogenated nonimmobilizing alkanes, such as 1,2-dichlorohexafluorocyclobutane and 2,3-dichlorooctafluorobutane, also fail to enhance GABAergic currents, but display specific behavioral effects that are distinct from those of structurally similar anesthetics. At concentrations predicted to be anesthetic, 1,2-dichlorohexafluorocyclobutane and 2,3-dichlorooctafluorobutane produce amnesia but fail to produce immobility. Neuronal nicotinic acetylcholine (nACh) receptors are sensitive to many anesthetics and are thought to have an important role in learning and memory. We postulated that neuronal nACh receptors might mediate the common amnestic action of nonhalogenated and perhalogenated alkanes. To test the hypothesis that neuronal nACh receptors have a role in mediating the behavioral effects of general anesthetics and nonimmobilizers, we quantified the inhibitory potencies of nonhalogenated anesthetic alkanes and perhalogenated nonimmobilizing alkanes on currents mediated by alpha(4)beta(2) neuronal nACh receptors. Our studies reveal that anesthetics and nonimmobilizers significantly inhibit alpha(4)beta(2) neuronal nACh receptors at concentrations that suppress learning and with potencies that correlate with their hydrophobicities. These results support the hypothesis that alpha(4)beta(2) neuronal nACh receptors mediate the amnestic actions of alkanes but not their immobilizing actions. IMPLICATIONS: The results of this study suggest that the immobilizing actions of general anesthetics do not result from the inhibition of alpha(4beta2) neuronal nicotinic acetylcholine receptors. However, the inhibition of neuronal nicotinic acetylcholine receptors may account for the amnestic activities of general anesthetics and nonimmobilizers.     

全身麻醉药促哺乳动物脑发育期神经元凋亡作用的实验研究进展

研究发现氯胺酮、咪达唑仑、N2O、异丙酚和异氟烷等全身麻醉药通过阻滞N-甲基-D-天冬氨酸受体(N-methyl-D-aspartate glutamate recepors,NMDAR)和/或过度激活γ-氨基丁酸受体(gamma aminobutyric acid receptors,GABAR)触发了发育期脑易感区神经元凋亡性退行型病变.这一凋亡现象表现为以下特点:①与给药时间呈正相关;②呈剂量依赖性;③药物的联合应用显著增强了凋亡效应;④与鼠龄存在显著的相关性.神经功能行为学实验证实这一凋亡将对日后的学习记忆功能产生持久的影响.     

How we recall (or don’t): the hippocampal memory machine and anesthetic amnesia

Purpose

The hippocampal formation occupies a central position for the processing of sensory input into learned, remembered, and consciously retrievable information. The mechanisms by which anesthetic drugs interfere with these processes are now emerging. We review the current understanding of the role of the hippocampal formation in the generation of memory traces and how anesthetics might interfere with its function.

Clinical features

Intraoperative amnesia is a desired endpoint of general anesthesia from the perspective of both the patient and the practitioner. “Intraoperative awareness with recall” can result when learning and memory do occur. In addition, anesthetics are capable of inducing a state of “conscious amnesia” that can provide insight into the workings of the brain and might be useful clinically.

Conclusions

Anesthesiologists routinely induce the most fascinating pharmacologic effects in existence, the reversible interference of anesthetics with higher cognitive functions. Understanding how the drugs in our custody exert their effects should be our contribution to mankind’s universal knowledge base.     

麻醉药对[Ca2＋]i的多途径改变及相关生物学效应

Ca2＋是细胞内的第二信使．它参与细胞内很多生理活动过程．包括神经递质释放．肌肉收缩,腺体分泌．学习记忆及细胞凋亡等。麻醉药可以通过多种方式直接或间接改变[Ca2＋]i从而对生物体产生错综复杂的影响．这些影响有些与麻醉作用有关有些与麻醉作用无关。