吸入麻醉药对中枢神经系统功能的影响

现今临床常用的吸入麻醉药如氧化亚氮、恩氟烷、异氟烷、七氟烷和地氟烷等在吸入麻醉过程中,皆会对患者的中枢神经系统和/或脑功能产生一定程度的影响.不同的药物,不同的吸入浓度和持续时间,对脑电活动抑制程度不同.吸入麻醉药与不同的静脉麻醉药联合应用,其脑功能受影响的特点也有所差异.此外,正常或疾病状态下的中枢神经系统和/或脑组织、脑电活动和血管功能,对各种吸入麻醉药的反应也不相互一致.详细了解临床常用的各种吸入麻醉药对脑功能影响的特点,掌握正确的使用方法,对颅脑和中枢神经系统疾病患者手术和麻醉安全尤为重要.本文结合近期国外相关文献,针对吸入麻醉药对脑电生理活动、脑血管自动调节功能、脑组织代谢功能和颅内压影响等手术和麻醉医生关心的热点问题,进行全面阐述,对临床工作有重要指导意义.     

七氟烷对新生大鼠海马caspase-3和磷酸化ERK表达的影响

目的评价磷酸化细胞外信号调节激酶(p-ERK)在七氟烷致新生大鼠海马神经细胞凋亡中的作用。方法出生7 d的健康清洁级雄性SD大鼠36只,体质量11～18 g,采用随机数字表法分为对照组(C组,n=18)和七氟烷麻醉组(S组,n=18)。C组每天同一时间吸入2 h的30%氧气;S组吸入2 h的3.4%七氟烷。2 d后处死大鼠采用Western blotting法检测活化caspase-3和p-ERK的表达。结果与C组比较,S组活化caspase-3的表达上调,p-ERK的表达下调(P0.05)。结论七氟烷通过下调p-ERK的表达促进新生大鼠海马神经细胞凋亡。     

中枢组胺能神经介导七氟烷麻醉后认知功能障碍的实验研究

目的分析中枢组胺能神经介导七氟烷麻醉与认知功能障碍的关系。方法选取健康雄性大鼠120只,对所有大鼠进行抑制性训练和记忆测试。将120只大鼠随机分为4组各30只。A组进行七氟烷麻醉,B组未进行麻醉,C组麻醉后在抑制性训练前注射荷包牡丹碱(BMI),D组麻醉后在记忆测试前注射BMI。实验结束后处死大鼠,检测大鼠组织蛋白水平及脑源性神经影响因子(BDNF)表达情况,分析4组大鼠在进行抑制性训练和记忆测试时进入潜伏期的情况。结果抑制性训练中A组大鼠进入潜伏期的时间明显长于B、C、D组(P0.05),而B、C、D组大鼠进入潜伏期的时间差异无统计学意义(P0.05)。记忆测试时,A组大鼠进入潜伏期的时间明显短于B组,D组大鼠进入潜伏期的时间明显短于C组(P0.05)。对比4组BDNF水平发现,A组BDNF表达水平明显低于其他3组(P0.05),B组BDNF表达水平明显高于C、D组(P0.05);C、D组间BDNF表达水平差异无统计学意义(P0.05)。结论七氟烷麻醉后认知功能障碍与中枢组胺能神经具有一定关系,激活组胺能神经可有效抑制七氟烷麻醉后对认知功能的损伤。     

不同吸入麻醉方式对局灶性大脑中动脉缺血-再灌注模型制作的影响

目的比较保留自主呼吸的面罩全身麻醉和气管插管呼吸机控制呼吸全身麻醉两种吸入麻醉方式对局灶性大脑中动脉缺血-再灌注大鼠模型制作过程中各项生理参数（血压、pH值、动脉血氧分压和二氧化碳分压、血糖、脑温、直肠温度）以及脑梗死病变的影响。方法采用健康雄性成年SD大鼠制作改良ZeaLonga局灶性大脑中动脉缺血-再灌注模型,室温20～22°C,相对湿度60%。先采用面罩吸入诱导麻醉,随后A组大鼠行气管插管吸入全身麻醉,由呼吸机控制呼吸;B组大鼠施以面罩吸入全身麻醉,保留自主呼吸。监测模型制作过程中大鼠平均动脉血压、动脉血氧分压和二氧化碳分压、pH值、血糖、脑温（皮质、纹状体）和直肠温度的变化;观察再灌注前30min、再灌注后24h和48h的神经功能缺损程度评分,以及再灌注后48h两组大鼠存活率和脑梗死范围的差异。结果动物模型制作过程中两组大鼠不同时限动脉血氧分压和二氧化碳分压、pH值及血糖水平的变化,组间差异无统计学意义（均P〉0.05）,但A组不同时限平均动脉血压高于B组,差异有统计学意义（均P〈0.05）;而再灌注前后脑温和直肠温度略低于B组,但差异无统计学意义（均P〉0.05）。两组再灌注前30min、再灌注后24h和48h神经功能缺损程度评分和再灌注后48h存活率差异无统计学意义（均P〉0.05）。再灌注后48h,A组大鼠梗死体积[（56.70±4.20）%]低于B组[（64.30±3.50）%],差异有统计学意义（t=-5.105,P=0.000）。结论吸入麻醉方式不同对局灶性大脑中动脉缺血-再灌注模型大鼠的脑温、直肠温度、pH值、血糖及动脉血氧分压和二氧化碳分压无明显影响,但可造成大鼠在手术过程中平均动脉血压和梗死范围的差异。     

术中镇静药物对颅内肿瘤继发癫痫患者皮层脑电的影响

目的探讨术中镇静药物对颅内肿瘤继发癫痫患者皮层脑电的影响,以期为颅内肿瘤继发癫痫手术中镇静药物的应用提供借鉴。方法以颞叶占位性病变伴癫痫患者为研究对象,将患者分为2组,予以外科手术切除肿瘤治疗,术中应用2种麻醉方式,A组:丙泊酚麻醉诱导;1%七氟烷吸入复合丙泊酚持续静脉泵入麻醉维持。B组:静注咪达唑仑麻醉诱导,其余同A组。病灶切除前;停用丙泊酚后10min;七氟烷控制在0.5 MAC下后;病灶切除后,这4个阶段均行ECoG监测,分析监测中暴发抑制(BS)发生率。结果 (1)停用丙泊酚前,BS发生率A组明显低于B组(P0.05);(2)停用丙泊酚前后比较,BS发生率无明显差异(P0.05);(3)七氟烷控制在0.5MAC下前后比较,BS发生率有显著差异(P0.05),七氟烷控制在0.5 MAC下前明显高于七氟烷控制在0.5 MAC下后;(4)B组病灶切除后1例患者出现BS,8例术中唤醒患者静脉推注丙泊酚时,7例(87.25%)出现BS。结论在颅内肿瘤继发癫痫患者,术中病灶监测时应使用丙泊酚行麻醉诱导,监测前10min左右停丙泊酚,监测时将七氟烷吸入浓度控制尽量低,以减少对术中病灶脑电图的影响。     

不同药物麻醉后大鼠全脑缺血脑温的变化

目的 了解不同常用麻醉药物后麻醉大鼠全脑缺血脑温的变化。方法 选用乌拉坦（1g/kg)、戊巴比妥钠（40mg/kg)、水合氯醛（400mg/kg)、巴比妥钠（300mg/kg)和苯巴比妥钠（200mg/kg)腹腔麻醉大鼠后全脑缺血测量脑组织温度的动态变化。结果 这些药物麻醉大鼠后行四动脉阻断全脑缺血，脑温进一步下降；但不同药物的作用各异。结论 本实验的结果说明了在脑缺血同一个实验过程中尽量避免使用不同各类的麻醉药物引起的脑温波动，进而影响实验结果的准确性。     

七氟烷对老年肺癌根治术后患者认知功能及焦虑抑郁的影响

目的 探讨老年肺癌根治术患者术中应用七氟烷麻醉的效果及对术后心理状态及认知功能的影响.方法 将本院83例欲行手术治疗的老年肺癌患者通过掷币法分为七氟烷麻醉组及丙泊酚麻醉组,其中丙泊酚麻醉组(n=41)术中给予丙泊酚麻醉维持,七氟烷麻醉组(n=42)术中给予七氟烷麻醉维持,对比两组患者手术效果、术后疼痛、焦虑抑郁情绪、血...     

依达拉奉调控PI3K/Akt信号通路抑制七氟烷致海马神经元凋亡

目的 探讨依达拉奉对七氟烷致海马神经元凋亡及对PI3K/Akt信号通路影响.方法 将80只成年昆明小鼠随机分为正常组、七氟烷组、七氟烷+依达拉奉组及LY294002+七氟烷+依达拉奉组,每组20只.正常组:小鼠不做处理;七氟烷组:小鼠每天给予1h吸入1.5％七氟烷;七氟烷+依达拉奉组:小鼠每天尾静脉注射依达拉奉3 mg...     

静吸复合麻醉对重症颅脑损伤患者脑氧代谢的影响

目的观察静吸复合麻醉对重症颅脑损伤患者脑氧代谢的影响。方法将80例重症颅脑损伤患者随机分为2组,对照组(n=40)靶控输注行丙泊酚+瑞芬太尼行静脉麻醉,观察组(n=40)靶控输注丙泊酚复合吸入七氟烷辅之以瑞芬太尼行静吸复合麻醉;比较2组患者不同时刻的血流动力学指标和脑氧代谢指标。结果观察组不同时刻的颈内静脉血氧饱和度(SjvO2)、桡动脉-颈内静脉血氧含量差(Da-jvO2)、脑氧摄取率(CERO2)与对照组比较差异具有统计学意义(P0.05)。结论静吸复合麻醉对重症颅脑损伤患者能够降低围术期的脑氧代谢率,发挥一定的脑保护作用。     

两种麻醉方法用于脊柱神经外科手术的比较研究

目的 比较七氟烷复合瑞芬太尼静脉吸入复合麻醉(吸入麻醉组)和丙泊酚复合瑞芬太尼全凭静脉麻醉(静脉麻醉组)对脊柱神经外科手术患者血糖和C-反应蛋白水平,以及术中运动诱发电位监测成功率的影响.方法 纳入患者分别以咪哒唑仑、丙泊酚、舒芬太尼、罗库溴铵进行诱导麻醉,瑞芬太尼持续静脉靶控输注维持术中镇痛;静脉麻醉组和吸入麻醉组患者分别采用丙泊酚持续静脉靶控输注和七氟烷吸入维持麻醉深度,记录围麻醉期平均动脉压、心率,观察血流动力学变化和运动诱发电位监测成功率.分别于麻醉诱导前、诱导后2 h、手术后24 h采集患者静脉血标本,检测血糖和C-反应蛋白水平变化.结果 麻醉期间不同观察时间点,两组患者血流动力学维持稳定,静脉麻醉组平均动脉压高于吸入麻醉组(均P＜0.05).麻醉诱导后60和120min,两组患者心率均低于麻醉诱导前基础值(P＜0.05),其中静脉麻醉组于麻醉诱导后5 min即开始出现心率下降,且低于吸入麻醉组(P＜0.05).同一观察时间点(组间比较)及麻醉诱导前后(组内比较)血糖水平差异均无统计学意义(均P＞0.05);但手术后24 h,两组患者血清C-反应蛋白水平均高于麻醉诱导前基础值(P＜0.05),且吸入麻醉组高于静脉麻醉组(P＜0.05).静脉麻醉组患者运动诱发电位监测成功率高于吸入麻醉组(均P＜0.05).结论 两种麻醉方法均能维持脊柱神经外科手术中血流动力学和血糖水平稳定,并抑制术中炎性应激反应,而对术后炎性应激反应无抑制作用.丙泊酚全凭静脉麻醉更适合术中运动诱发电位监测.     

The effects of anesthetics on the concentrations of cholecystokinin octapeptide sulfate-like immunoreactivity in rat brain regions

Cholecystokinin octapeptide sulfate-like immunoreactivity (CCK-8S-LI) was determined by radioimmunoassay in rat brain areas following injections of pentobarbital, halothane and chloral hydrate. Time-dependent changes in the concentrations of CCK-8S-LI were different between pentobarbital and chloral hydrate in all brain regions studied. After pentobarbital injection, CCK-8S-Li peaked at 30-60 min in the frontal cortex, nucleus accumbens, striatum and substantia nigra; after chloral hydrate injection, CCK-8S-LI peaked at 120 min in the hypothalamus, nucleus accumbens and substantia nigra. Both anesthetics induced almost the same sleeping times. Halothane inhalation caused increases in the concentrations of CCK-8S-LI in the amygdala and hippocampus. In addition, following intracardial perfusion of saline for 30 min after pentobarbital anesthesia, the concentrations of CCK-8S-LI increased in the nucleus accumbens, and decreased in the frontal cortex. These results suggest that since different anesthetics cause different changes in CCK levels, anesthetics affect studies of these neurons.     

Influence of anaesthetics on rat striatal dopamine metabolism in vivo

The effects of 4 anaesthetics, halothane, α-chloralose, chloral hydrate and pentobarbitone, on rat striatal extracellular dihydroxyphenylacetic acid (DOPAC) levels were determined using in vivo voltammetry. Stable baseline levels of DOPAC were maintained under halothane/N ₂O and α-chloralose while the extracellular levels of DOPAC gradually declined under chloral hydrate or pentobarbitone anaesthesia. Administration of haloperidol (0.3 mg/kg i.p.) significantly increased DOPAC using halothane/N ₂O, α-chloralose or chloral hydrate but not under pentobarbitone anaesthesia. The greatest increase in DOPAC was seen in rats anaesthetized with α-chloralose>halothane/N₂O>chloral hydrate > pentobarbitone. Apomorphine (0.5 mg/kg s.c.) given 2 h after haloperidol partially reversed the increase in DOPAC produced by haloperidol. The results suggest care needs to be exercised in the choice of anaesthetic used for voltammetric studies with pentobarbitone being the least recommended.     

Chloral hydrate anesthesia alters the responsiveness of central serotonergic neurons in the cat

The influence of chloral hydrate anesthesia on the spontaneous activity and responsiveness of serotonergic neurons was examined by administering chloral hydrate (300 mg/kg, i.p.) to freely moving cats from which serotonergic unit activity in the dorsal raphe nucleus (DRN) was being recorded. Although chloral hydrate administration produced a surgical level of anesthesia within 15 min following injection, it produced only a small decrease ( 20%) in the spontaneous activity of DRN serotonergic neurons. In contrast, the responsiveness of these same neurons was greatly altered by chloral hydrate administration. By examining the same neuron before and after chloral hydrate injection, it was found that chloral hydrate anesthesia completely abolished the excitatory responses of DRN serotonergic neurons to auditory and visual stimuli, as well as their excitatory response to electrical stimulation of the gigantocellular tegmental field (FTG) in the pontine reticular formation. On the other hand, the inhibition of serotonergic neuron firing resulting from systemic administration of WB 4101 (1.0 mg/kg, i.p.), a selective α₁ adrenergic receptor antagonist, was greatly potentiated by chloral hydrate anesthesia. Therefore, these data indicate that chloral hydrate anesthesia produces profound changes in the physiological and pharmacological responses of central serotonergic neurons which are not predictable by examination of spontaneous activity alone. Furthermore, as discussed, if it not clear to what extent these confounding influences might generalize to other anesthetized or immobilized preparations. Thus, beyond the obvious advantage which allows for the study of relationships between neuronal activity and behavior, single unit studies conducted in awake, freely moving animals also may be of greater value for basic physiological and pharmacological studies.     

Ethanol stimulates the firing rate of nigral dopaminergic neurons in unanesthetized rats

In unanesthetized paralyzed rats, i.v. ethanol administration (0.5–2.0 g/kg) increased (by 30–120%) the firing rate of dopaminergic (DA) neurons in the substantia nigra, pars compacta. Doses of 4.0 g/kg or higher produced an initial stimulation followed by a long-lasting inhibition of firing. On the contrary, in rats anesthetized with halothane (2.5% v/v in air) or with chloral hydrate (400 mg/kg), doses of ethanol up to 2 g/kg failed to activate DA neurons, while a dose of 4 g/kg inhibited neuronal firing without the initial stimulant response. In unanesthetized-curarized rats, the i.v. administration of either chloral hydrate (100–400 mg/kg) or pentobarbital (10–40 mg/kg) or the inhalation of halothane (0.5–2.5% v/v in air) produced a dose-dependent increase in the firing rate of DA neurons. However, the maximum increase produced by these anesthetics was less pronounced and lasting than that produced by ethanol.     

Acute haloperidol increases impulse activity of brain noradrenergic neurons

Haloperidol (0.5 mg/kg, i.p.) increased impulse activity of every noradrenergic locus coeruleus neuron tested in chloral hydrate anesthetized rats. Mean discharge rate increased from 1.4 ± 0.2 Hz before to 2.7 ± 0.4 Hz at 45 min after injection, with significantly increased activity occurring by 15 min post-drug. Elevated activity was apparent for at least 2 h following haloperidol. These results reveal that haloperidol has profound effects on brain noradrenergic neurons, indicating a possible site of action for effects of this neuroleptic agent.     

Bursting as a source of non‐linear determinism in the firing patterns of nigral dopamine neurons

Nigral dopamine (DA) neurons in vivo exhibit complex firing patterns consisting of tonic single‐spikes and phasic bursts that encode information for certain types of reward‐related learning and behavior. Non‐linear dynamical analysis has previously demonstrated the presence of a non‐linear deterministic structure in complex firing patterns of DA neurons, yet the origin of this non‐linear determinism remains unknown. In this study, we hypothesized that bursting activity is the primary source of non‐linear determinism in the firing patterns of DA neurons. To test this hypothesis, we investigated the dimension complexity of inter‐spike interval data recorded in vivo from bursting and non‐bursting DA neurons in the chloral hydrate‐anesthetized rat substantia nigra. We found that bursting DA neurons exhibited non‐linear determinism in their firing patterns, whereas non‐bursting DA neurons showed truly stochastic firing patterns. Determinism was also detected in the isolated burst and inter‐burst interval data extracted from firing patterns of bursting neurons. Moreover, less bursting DA neurons in halothane‐anesthetized rats exhibited higher dimensional spiking dynamics than do more bursting DA neurons in chloral hydrate‐anesthetized rats. These results strongly indicate that bursting activity is the main source of low‐dimensional, non‐linear determinism in the firing patterns of DA neurons. This finding furthermore suggests that bursts are the likely carriers of meaningful information in the firing activities of DA neurons.     

Regional studies of blood-brain barrier transport of glucose and leucine in awake and anesthetized rats

D-Glucose and L-leucine are transported across the blood-brain barrier (BBB) by two separate carrier-mediated facilitated diffusion mechanisms. In the awake rat there are regional differences in blood-to-brain glucose transport among the cerebral cortex, cerebellum, hippocampus, and striatum. To determine whether these are due to variations in the regional density or affinity of the glucose transporter moiety of brain capillaries or are secondary to regional tissue perfusion and capillary arrangement characteristics, we studied regional blood-to-brain transport of L-leucine in awake rats; regional blood-to-brain transport of both glucose and leucine under chloral hydrate anesthesia, a condition associated with altered regional brain blood flow (BF) and metabolism; and regional brain vascular volume, derived from the L-glucose and insulin spaces, in both awake and anesthetized rats. We found the same regional differences in blood-to-brain leucine transport in awake rats as we previously described for D-glucose transport. These regional differences in glucose and leucine transport disappear under chloral hydrate anesthesia, as regional differences in BF are abolished. However, we found regional differences in the brain vascular volumes, which are evident in wakefulness and persist during anesthesia. These results suggest that the regional differences in blood-to-brain transport are due mainly to local tissue perfusion and capillary arrangement characteristics rather than to intrinsic regional differences in the transport systems of the BBB.     

Voltammetry in the striatum of chronic freely moving rats: Detection of catechols and ascorbic acid

Differential pulse voltammetry used in combination with an electrochemically treated carbon fiber electrode allowed to detect ascorbic acid (AA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum of unanaesthetized freely moving rats. Carbon fiber electrodes were implanted under light halothane anaesthesia. When the rat recovered from anaesthesia, voltammograms were recorded every 2.5 min for about 5 h. During the last 3 h the signals corresponding to AA and DOPAC appeared stable and reproducible, allowing comparisons between control and pharmacological experiments. After the in vivo experiments, the electrodes were calibrated in AA and DOPAC solutions. Striatal AA and DOPAC levels were thus estimated to be 306 and 17.7 μM respectively. DOPAC signals were increased by haloperidol and chloral hydrate, decreased by amphetamine and suppressed by pargyline. In pargyline pretreated rats the catechol signal slightly re-appeared after amphetamine injections. This signal was attributed to dopamine (DA) and estimated to a concentration50NM DA. The AA current recorded in the striatum was not modified when dopaminergic terminals selectively degenerated. The AA signal was decreased by chloral hydrate or halothane anaesthesia and increased by amphetamine injections. This latter effect depended on the presence of dopaminergic terminals. This shows that the increasing current effect of amphetamine, previously observed by non-selective techniques, should be attributed to AA rather than DA. These results confirm that the catechol compound electrochemically detected in the striatum is the direct metabolite of the DA, i.e. DOPAC, and support the thesis of a functional relationship between AA levels and dopaminergic neurotransmission.     

Anti-serotonergic effects of urethane and chloral hydrate may not be mediated by a blockade of 5-HT2 receptors

Summary The general anesthetics urethane and chloral hydrate have profound anti-serotonergic effects both in the rat cortex in vivo and the rat aortic ring in vitro. The suggestion that these effects may be due to an action on 5-HT₂ receptors was tested using ex vivo and in vitro [³H]ketanserin binding assays with membrane-enriched fractions from rat brain. Urethane did not alter [³H]ketanserin binding in the ex vivo assay. In the in vitro assay, urethane, chloral hydrate, and its active metabolite 2,2,2-trichloroethanol produced slight reductions (of 16%, 9%, and 18%, respectively) of [³H]ketanserin binding. These studies suggest that anti-serotonergic effects of urethane and chloral hydrate may not be mediated by a blockade of 5-HT₂ receptors.     

Ethanol increases single unit activity in the inferior olivary nucleus

Single unit recording of rat inferior olivary nucleus neurons reveals significantly elevated discharge after acute intraperitoneal injection of 2 g/kg ethanol. This effect is consistent across 3 different methods of anesthesia and immobilization: local Xylocaine plus intraperitoneal D-tubocurare, intraperitoneal chloral hydrate and halothane vapor. In contrast, under urethane anesthesia acute ethanol produces significant depression of olivary discharge. Since this effect is opposite to that found under the other anesthetic conditions (including topical Xylocaine only), urethane anesthesia may compromise generalizations of electrophysiologic studies of ethanol. Neurons of the inferior olivary nucleus excite cerebellar Purkinje cells through a powerful afferent circuit; our data therefore suggest that ethanol-induced increases in cerebellar Purkinje cell complex (climbing fiber burst) spikes, obtained in our previous studies, are secondary to olivary activation.