内侧视前区毁损对异丙酚及氯胺酮麻醉作用的影响

目的 观察毁损前下丘脑的内侧视前区(mPOA)对静脉麻醉药异丙酚、氯胺酮诱发大鼠翻正反射消失潜伏期(RL)、恢复时间(RT)的影响,探讨mPOA在异丙酚、氯胺酮麻醉作用机制中的地位。方法 24只SD大鼠,随机分为两组,每组12只,即mPOA微量注射NS组(NS组),甲基天冬氨酸(NMDA)毁损组(NMDA-des组);7 d后再将其各分为两个亚组,即NS+异丙酚组,NS+氯胺酮组,NMDA-des+异丙酚组,NMDA-des+氯胺酮组。微量注射NMDA(5μg/0.2μl)毁损大鼠mPOA后,观察大鼠行为学和体重的变化;7 d后分别腹腔注射异丙酚(100mg·kg-1)和氯胺酮(100mg·kg-1),观察对大鼠翻正反射消失潜伏期和恢复时间的影响。结果 mPOA微量注射NS组大鼠行为学及体重无明显变化,NMDA毁损组与NS组比较体重显著减轻(P<0.01);腹腔注射异丙酚或氯胺酮后,毁损组大鼠RL较NS组均显著延长(P<0.01),RT显著缩短(P<0.01,P<0.05)。结论 mPOA可能参与了对异丙酚、氯胺酮麻醉作用的调节。     

硬膜外麻醉下异丙酚联合咪达唑仑镇静对内隐记忆的影响

目的探讨术中异丙酚联合咪达唑仑镇静对内隐记忆的影响,分析内隐记忆消失的中潜伏期听觉诱发电位(MLAEP)参数界值,为临床镇静深度监测提供一项新的客观指标。方法 硬膜外麻醉下择期手术病人45例(ASA Ⅰ～Ⅱ级),随机分为异丙酚组(P)、联合用药一组(PM1)、联合用药二组(PM2)3组,每组15例。P组:异丙酚2 mg·kg-1·h-1;PM1组:异丙酚1.5 mg·kg-1·h 咪达唑仑0.03 mg·kg-1·h-1;PM2组:异丙酚1.5 mg·kg-1·h-1 咪达唑仑0.06 mg·kg-1·h-1。所有病人经异丙酚或异丙酚联合咪达唑仑镇静15 min后,让病人听录音带即内隐记忆刺激。记录入室时(T1)、行硬膜外麻醉后(T2)、静脉给药后15min(T1)、切皮后2min(T4)、内隐记忆刺激完成即刻(T5)等时点的心率(HR)、平均动脉压(MAP)、MLAEP。术后6 h进行记忆调查,测定病人的模糊辨听率。结果 异丙酚镇静Pa、Nb波潜伏期延长、波幅降低(P<0.05),但联合用药组潜伏期延长更明显、波幅降得更低(P<0.05)。所有病人外显记忆均消失;P组均存在内隐记忆,两联合用药组内隐记忆均消失。结论异丙酚和咪达唑仑联合镇静可以消除外显记忆和内隐记忆。MLAEP参数Pa、Nb波潜伏期、波幅可以作为评价术中镇静深度的客观监测指标。     

异丙酚对β-淀粉样蛋白诱导大鼠皮层神经元损伤的影响

目的 探讨异丙酚对β-淀粉样蛋白(β-AP)诱导大鼠皮层神经元损伤的影响.方法 孕18 dSD大鼠,体外分离皮层神经元,5×104个/孔,每孔200μl接种于96孔培养板上,培养7 d.实验一:取15孔神经元随机分为5组(n=3):对照组;损伤组;异丙酚预防给药Ⅰ组加入β-AP 25μmol/L前24 h加入异丙酚50μmol/L,再孵育24h;异丙酚预防给药Ⅱ组同时加入异丙酚50 μmol/L和β-AP 25μmol/L,孵育24 h;异丙酚治疗给药组加入β-AP 25μmol/L后6 h,加入异丙酚50μmol/L,再孵育18 h.实验二:取18孔神经元随机分为6组(n=3):对照组;损伤组;脂肪乳剂组加入β-AP 25μmol/L后6 h,加入等容量10%脂肪乳剂,再孵育18 h;不同浓度异丙酚组加入β-AP 25μmol/L后6 h,分别加入异丙酚1、10、50 βmol/L,再孵育18 h.测定神经元乳酸脱氢酶(LDH)释放量和神经元活力.采用TUNEL法、Hoechst33342染色观察细胞凋亡情况,计算细胞凋亡率.结果 实验一:与损伤组比较,异丙酚预防给药组LDH释放量差异无统计学意义(P＞0.05),异丙酚治疗给药组神经元LDH释放量减少(P＜0.05).实验二:与损伤组比较,异丙酚50μmol/L组神经元LDH释放量减少,神经元活力升高,细胞凋亡率降低(P＜0.05).结论 异丙酚50 μmol/L治疗性给药可减轻β-淀粉样蛋白诱导大鼠皮层神经元损伤,预防性给药对其无影响.     

腹腔注射小剂量氯胺酮对小鼠吗啡诱发急性瘙痒的影响

目的 观察小剂量氯胺酮对小鼠吗啡诱发急性瘙痒的作用. 方法 40只雄性C57/BL6小鼠按完全随机分组方法分为5组(每组8只):空白对照组(C组),鞘内注射生理盐水5μl;吗啡组(M组),鞘内注射1.0 nmol吗啡5 μl;生理盐水对照组(N组),鞘内注射1.0 nmol吗啡5μl,5 min后腹腔注射5 mg/kg生理盐水;氯胺酮给药组(K组):鞘内注射1.0 nmol吗啡5μl,5 min后腹腔注射5 g/L氯胺酮;氯胺酮对照组(KC组):鞘内注射5μl生理盐水后腹腔注射5g/L氯胺酮.以5 min为间隔记录小鼠40 min内搔抓次数. 结果 与C组比较,M组小鼠搔抓次数明显增加,0～5 min小鼠开始出现搔抓反应[(5.0±1.2)次],6 min～10 min搔抓反应达到高峰期[(13.1±1.9)次],随后减少,持续约40 min;与N组比较,K组搔抓次数在6 min～10min[(4.8±1.4)次]、11 min～15 min[(4.1±1.2)次]、16min～20 min[(2.2±0.7)次]均有不同程度的下降(P＜0.05);与KC组比较,K组搔抓次数除31 min～40 min外,差异均有统计学意义(P＜0.05).腹腔注射氯胺酮后K组搔抓次数明显减少(P＜0.05).结论 腹腔注射小剂量氯胺酮能在一定程度上缓解小鼠吗啡诱发的急性瘙痒.     

氯胺酮预给药对体外谷氨酸诱导大鼠小脑颗粒神经元凋亡的影响

目的探讨氯胺酮预给药对谷氨酸诱导大鼠小脑颗粒神经元(CGNs)凋亡的作用及信号转导机制。方法将原代培养的大鼠CGNs随机分为8组:C组:培养基中不加药液;G组:培养基中加入300 μmol/L谷氨酸;K1、K2、K3组:培养基中分别加入10、100、1 000μmol/L氯胺酮预先孵育1 h 后,再加入谷氨酸;LK3组:培养基中加入20μmol/L Ly294002,30min后加入1 000μmol/L.氯胺酮,1 h后加入谷氨酸;L组:培养基中加入Ly294002;LG组:培养基中加入Ly294002,30 min后加入谷氨酸。20 h后,用相差显微镜观察神经元形态学,Hoechst33258核染色后,观察凋亡CGNs;提取DNA行琼脂糖凝胶电泳分析,二乙酸荧光素染色法测定CGNs的存活率。结果谷氨酸可诱导大鼠CGNs凋亡。CGNs 存活率:与G组比较,C组、K1、K2、K3、L组升高幅度下降(P<0.05),LG组差异无统计学意义;C组与L组比较差异无统计学意义;LK3组低于K3组(P<0.01)。CGNs存活率(Y)与氯胺酮浓度(X)呈线性回归,回归方程为Y=0.202logX 0.2596,r3=0.919(P<0.01)。结论氯胺酮剂量依赖性地抑制谷氨酸诱导大鼠CGNs的凋亡,而PI3-K/AKT信号转导通路可能参与了其抗神经元凋亡作用。     

脊髓阿片受体在异丙酚对大鼠抗伤害性效应中的作用

目的 探讨脊髓阿片受体在异丙酚对大鼠抗伤害性效应中的作用.方法 雄性SD大鼠,体重220～280 g,选取鞘内置管成功的大鼠90只,随机分为9组(n=10):P组、D组和A组分别鞘内注射异丙酚10μg、二甲基亚砜(DMSO)5μl,人工脑脊液5μl;PN组和DN组分别鞘内注射异丙酚10μg、DMSO 5μl,5 min后均鞘内注射纳洛酮15 μg;PC组和DC组分别鞘内注射异丙酚10 μg、DMSO 5 μl,5 min后均鞘内注射高选择性μ受体拮抗剂CTOP 1 μg,PI组和DI组分别鞘内注射异丙酚10μg和DMSO 5 μl,5 min后均鞘内注射高选择性δ受体拈抗剂ICI 174,864 1μg.于首次给药前(T0)、首次给药后10 min(T1)、20 min(T2)、40 min(T3)时采用热水缩尾法测定痛阈,并计算痛阈提高百分率.结果 与T0时比较,T1,2时P组、PN组、PI组和PC组痛阈升高(P<0.05);P组痛阈高于D组,PN组痛阈高于DN组,PI组痛阈高于DI组,PC组痛阈高于DC组(P<0.05);与T1和T2时比较,T3时P组、PN组、PC组和PI组痛阈提高百分率降低(P<0.05);与P组和PC组比较,PN组和PI组首次给药后痛阈提高百分率降低(P<0.05).结论 异丙酚通过大鼠脊髓δ受体介导产生抗伤害性效应.     

慢性吗啡耐受大鼠脊髓背角神经元磷酸化突触素Ⅰ表达的变化

目的 观察慢性吗啡耐受大鼠脊髓背角神经元磷酸化突触素Ⅰ(p-Synapsin Ⅰ)表达的变化.方法 雄性SD大鼠45只,体重150～180 g,月龄1～2月,随机分为5组(n=9):假手术组(S组)、生理盐水组(NS组)、吗啡组(M组)、氯胺酮组(K组)和吗啡+氯胺酮组(M+K组).除S组外,所有大鼠均行鞘内置管,恢复3 d后鞘内给药,NS组给予生理盐水40 μl,M组给予吗啡20 μg,K组给予氯胺酮30μg,M+K组分别给予吗啡20μg及氯胺酮30 μg,2次/d,连续7 d.于给药前(T_0,基础状态)、给药后1、3、5、7 d及停药后1d(T_(1～5))时测定机械缩爪阈值(PWT)与热缩爪潜伏期(PWL),最后一次测定痛阈后处死大鼠,取L3～6脊髓背角,测定p-Synapsin Ⅰ(Ser603)的表达.结果 与基础值比较,M组T_(1,2)时PWT升高,T_(4,5)时PWT降低,T1～3时PWL延长,T_5时PWL缩短,M+K组T_(1～5),时PWT升高,PWL延长(P＜0.05).与S组和NS组比较,M组T_(1,2)时PWT升高,T_(4,5)时PWT降低,T1～3时PWL延长,T_5时PWL缩短,M+K组T_(1～5),时PWT升高,PWL延长(P＜0.05),K组PWT和PWL差异无统计学意义(P＞0.05).与M组比较,M+K组T_(2～5)时PWT升高,T_(3～5)时PWL延长(P＜0.05).与S组和NS组比较,M组和M+K组p-Synapsin Ⅰ(Ser603)表达上调(P＜0.05),K组p-Synapsin Ⅰ(Ser603)表达差异无统计学意义(P＞0.05);与M组比较,M+K组p-Synapsin Ⅰ(Ser603)表达下调(P＜0.05).结论 脊髓背角神经元Synapsin Ⅰ的磷酸化参与了大鼠慢性吗啡耐受的形成,吗啡促进Synapsin Ⅰ磷酸化的部分机制与激活N-甲基-D-天冬氨酸受体有关.     

氯胺酮复合咪达唑仑对谷氨酸诱导PC12细胞凋亡的影响

目的 探讨氯胺酮复合咪达唑仑对谷氨酸诱导PC12细胞凋亡的影响.方法 诱导分化4 d的神经元样PC12细胞随机分为5组:对照组(c组);谷氨酸组(Glu组)加入20 mmol/L谷氨酸;氯胺酮组(K组)、咪达唑仑组(M组)、氯胺酮+咪达唑仑组(K+M组)均加入20 mmol/L谷氨酸后,分别加入50 μmol/L氯胺酮、1μmol/L咪达唑仑、50 μmol/L氯胺酮+1 μmol/L咪达唑仑.各组细胞继续培养24 h后采用MTT法检测细胞活力,Hoechst33258核染色法及Annexin V-FITC/PI双染流式细胞术检测凋亡细胞.结果 与C组比较,Glu组细胞活力降低,细胞凋亡率升高(P<0.01);与Glu组比较,K组和M组细胞活力升高,细胞凋亡率降低(P<0.05);与K组和M组比较,K+M组细胞活力升高,细胞凋亡率降低(P<0.05);K组和M组细胞活力及细胞凋亡率差异无统计学意义(P>0.05).结论 氯胺酮复合咪达唑仑可更有效地抑制谷氨酸诱导PC12细胞凋亡.     

延髓头端腹内侧核GABA_A受体在异丙酚致大鼠痛觉过敏中的作用

目的 探讨延髓头端腹内侧核γ-氨基丁酸A亚型(GABA_A)受体在异丙酚致大鼠痛觉过敏中的作用.方法 清洁级SD大鼠64只,雌雄不拘,月龄2～3月,体重250～300 g,随机分为4组(n=16):溶媒对照组(C组)、异丙酚组(P组)、荷包牡丹碱组(B组)及荷包牡丹碱+异丙酚组(BP组).参照脑立体定位图谱定位大鼠延髓头端腹内侧核,C组注射人工脑脊液(荷包牡丹碱溶媒)0.4 μl,5 min后注射二甲基亚砜(异丙酚溶媒)0.4μl,P组注射异丙酚0.4μl(4μg),B组注射荷包牡丹碱0.4μl(10 ng),BP组注射荷包牡丹碱0.4 μl(10 ng),5 min后注射异丙酚0.4 μl(4 μg),各药物均在30 s内注射完毕,30 s后拔针.各取8只大鼠分别进行热板实验和福尔马林实验,记录热痛阈、福尔马林疼痛评分及其第1时相和第2时相累计疼痛评分.结果 热板实验中,P组热痛阈低于C组,BP组给药后20 min时热痛阈明显高于P组(P<0.05或0.01),其余时点差异无统计学意义(P>0.05).福尔马林实验中,P组福尔马林疼痛评分高于C组,BP组各时点福尔马林疼痛评分和第1、2时相累计疼痛评分均明显低于P组(P<0.05或0.01).结论 延髓头端腹内侧核GABA_A受体部分介导了异丙酚致大鼠痛觉过敏作用.     

异丙酚对兔离体气管平滑肌细胞内游离钙离子浓度的影响

目的 评价异丙酚对兔离体气管平滑肌细胞内游离钙离子浓度([Ca2+]i)的影响.方法 采用急性酶分离方法分离兔气管平滑肌细胞,采用随机数字表法,将细胞随机分为3组(n=5):异丙酚组(Ⅰ组,终浓度300 μmol/L)、异丙酚(终浓度300 μmol/L)+2-氨乙基硼酸二苯酯(终浓度40μmol/L)(Ⅱ组)和异丙酚(300 μmol/L)+斯里兰卡肉桂碱(终浓度10 μmol/L)(Ⅲ组).Ⅰ组加入终浓度300 μmol/L的异丙酚,孵育15 min后,用无钙的Hank平衡盐溶液冲洗3次,加入1μmol/L乙酰胆碱,记录[Ca2+]i.Ⅱ组加入终浓度40μmol/L的2-氨乙基硼酸二苯酯孵育15 min后,再加入终浓度为300μmol/L的异丙酚,与2-氨乙基硼酸二苯酯共同孵育15 min后,用无钙的Hank平衡盐溶液冲洗3次,加入1 μmol/L的乙酰胆碱.Ⅲ组加入终浓度10 μmol/L的斯里兰卡肉桂碱孵育15 min后,再加入终浓度为300μmol/L的异丙酚,与斯里兰卡肉桂碱共同孵育15 min后,用无钙的Hank平衡盐溶液冲洗3次,再加入1 μmol/L的乙酰胆碱.通过负荷钙离子荧光指示剂Fluo-3/AM测定气管平滑肌细胞内[Ca2+]i.结果 与Ⅰ组比较,Ⅱ组气管平滑肌细胞内[Ca2+]i差异无统计学意义(P＞0.05),Ⅲ组[Ca2+]i明显降低(P＜0.05).结论 异丙酚可降低兔离体气管平滑肌细胞内[Ca2+]i,其机制可能与抑制内质网1,4,5-三磷酸肌醇通路有关,而与内质网兰诺定通路无关.     

MID-LATENCY AUDITORY EVOKED POTENTIALS DURING KETAMINE ANAESTHESIA IN HUMANS

We studied mid-latency auditory evoked potentials (MLAEP) duringinduction of general anaesthesia with ketamine 2 mg kg^–1MLAEP were recorded before, during and after induction of generalanaesthesia on the vertex (positive) and mastoid (negative)positions. Latencies of the peak V, Na, Pa, Nb, P1 and amplitudesNa/Pa, Pa/Nb and Nb/P1 were measured. Fast-Fourier transformationwas used to calculate power spectra of the MLAEP. In the awakestate, MLAEP had large peak-to-peak amplitudes and a periodicwaveform. Peak latencies remained within the normal range. Powerspectra indicated high energy in the 30–40 Hz frequencyrange. After induction of general anaesthesia with ketamine,there was no change in latency of peaks V. Na, Pa, Nb, P1 andno apparent reduction in amplitudes Na/Pa, Pa/Nb and Nb/P1.In the power spectra, frequencies in the range of 30–40Hz retained high energy. Amplitudes and latencies of MLAEP didnot change during induction of general anaesthesia with ketamine.Primary processing of auditory stimuli in the primary auditorycortex seemed to be preserved under ketamine. Suppression ofsensory (auditory) information processing must take place ata higher cortical level in a dissociative manner. (Br. J. Anaesth.1993; 71: 629–632)     

Midlatency auditory evoked potentials and motor signs of wakefulness during anaesthesia with midazolam

We have studied midlatency auditory evoked potentials (MLAEP) and motor signs of wakefulness during anaesthesia with midazolam in 10 patients undergoing elective laparotomy under continuous extradural analgesia. Anaesthesia was induced with midazolam 0.3 mg kg-1 and maintained with midazolam 0.3-0.9 mg kg-1 h-1. Motor signs of wakefulness were documented as spontaneous movements and movements after simple commands (open eyes or move arms). MLAEP were recorded continuously awake, and during anaesthesia until the end of anaesthesia. Latencies of the peaks V, Na, Pa, Nb and P1 (ms) and amplitudes of the peaks Na/Pa, Pa/Nb and Nb/P1 (microV) were measured. Twenty-five movements were observed during anaesthesia; 15 movements in six patients were in response to commands. In two patients supplementary isoflurane was given. Latencies of the MLAEP peaks Pa, Nb and P1 increased slightly during anaesthesia. Amplitudes for Na/Pa, Pa/Nb and Nb/P1 did not change significantly. The high incidence of motor signs of wakefulness associated with preserved MLAEP indicated a high level of cortical neural activity and none of the MLAEP variables predicted movement during anaesthesia with midazolam.      

Effects of sevoflurane on mid-latency auditory evoked potentials and the 95% spectral frequency limit

OBJECTIVES: To investigate the effects of sevoflurane on mid-latency auditory evoked potentials (MLAEP) and compare them to changes in the encephalographic 95% spectral edge frequency (SEF95). PATIENTS AND METHODS: The effect of sevoflurane on MLAEP and SEF95 was studied in 15 patients. Anesthetic induction was carried out with propofol, remifentanil, and cisatracurium. After anesthetic induction, the patients were ventilated to achieve different expired concentrations of sevoflurane (1%, 1.5%, and 2%) during 3 consecutive 10-minute periods before the start of surgery. SEF95 and the amplitude and latency of the Na, Pa and Nb MLAEP waves were recorded. All the parameters were measured at baseline and during the different expired fractions of sevoflurane. RESULTS: The increase in sevoflurane concentration was accompanied by a significant decrease in amplitude and a statistically significant increase in latency of the Na, Pa and Nb waves. Likewise, SEF95 decreased significantly. A linear relation was demonstrated between sevoflurane concentration and the variables Na, Pa, Nb and SEF95. CONCLUSIONS: Our results indicate that the effect of sevoflurane on the MLEAP of Na, Pa and Nb is similar to that of other anesthetic gases. Even though the amplitude of the Na, Pa and Nb waves decreased in a dose-dependent way, SEF95 correlated more strongly with sevoflurane concentration.     

Effects of benzodiazepines on mid-latency auditory evoked potentials

Midlatency auditory evoked potentials (MLAEP) reflect primary cortical processing of auditory stimuli. The effects of benzodiazepines on MLAEP have not yet been studied. We examined the effects of intravenous induction of general anaesthesia using the benzodiazepines midazolam, diazepam and flunitrazepam on MLAEP in 30 patients scheduled for minor gynaecological procedures. Anaesthesia was induced with midazolam (0.2–0.3 mg · kg⁻¹, Group I, n = 10), diazepam (0.3–0.4 mg · kg⁻¹, Group II, n = 10) or flunitrazepam (0.03–0.04 mg · kg⁻¹, Group III, n = 10). Auditory-evoked potentials were recorded before and five to ten minutes after induction of general anaesthesia. Latencies of the peak V, Na, Pa, Nb and P1 (ms) and amplitudes Na/Pa, Pa/Nb and Nb/ P1 (μV) were measured. In the awake state, MLAEP had high peak to peak amplitudes and a periodic waveform. After induction of anaesthesia there was no or only a small increase in latencies of the peaks Na, Pa, Nb and P1, which was significant only for P1 in the midazolam group. Amplitudes Na/ Pa, Pa/Nb and Nb/P1 decreased only slightly and which reached statistical significance only for Na/Pa in the flunitrazepam group. The MLAEPs do not change markedly in amplitude or latency during induction of general anaesthesia with benzodiazepines. Primary cortical processing of auditory stimuli seems to be preserved under benzodiazepines. This may be seen in connection with cases of intraoperative awareness and especially the perception of auditory stimuli during anaesthetic regimens where benzodiazepines are used to suppress consciousness. Les potentiels évoqués auditifs de latence médiane (MLAEP) reflètent le premier processus de traitement cortical du stimulus auditif. Nous avons étudiés les effets de l’induction de l’anes-thésie générale intraveineuse avec les benzodiazépines midazolam, diazepam et flunitrazépam sur les MLAEP chez 30 patientes programmées pour des interventions gynécologiques mineures. L’induction anesthésique est réalisée par le midazolam (0,2–0,3 mg · kg⁻¹, groupe I, n = 10), le diazépam (0,3–0,4 mg · kg⁻¹, group II, n = 10) ou le flunitrazepam (0,03–0,04 mg · kg⁻¹, groupe III, n = 10). Les potentiels auditifs sont enregistrés avant et cinq ou dix minutes après l’induction de l’anesthésie générale. La latence des pointes V, Na, Pa, Nb et P1 (ms) et l’amplitude Na/Pa, Pa/Nb et Nb/P1 (μv) sont mesurées. A l’état vigile, les MLAEP ont des amplitudes de pointe élevées et une forme d’onde périodique. Après l’induction anesthésique, il n’y a pas d’augmentation ou une légère augmentation des pointes Na, Pa, Nb et P1, qui est significative pour P1 seulement dans le groupe midazolam. L’amplitude de Na, Pa, Nb et P1 diminue légèrement. Cette diminution n’est significative que pour Na/Pa avec le groupe flunitrazépam. Les MLAEP ne présentent vraiement pas de variations en amplitude et en latence pendant l’induction de l’anesthésie générale avec les benzodiazépines. Ceci peut être en rapport avec un état de veille peropératoire et spécialement avec la perception de stimuli auditifs pendant les techniques anesthésiques qui font appel aux benzodiazépines pour produire l’inconscience.     

Akustisch evozierte Potentiale mittlerer Latenz während Anästhesie mit Sufentanil

Patients and methods. We have studied mid-latency auditory evoked potentials (MLAEP) during general anaesthesia with sufentanil in ten patients scheduled for elective major urological surgery. Anaesthesia was induced with sufentanil 2–3?μg/kg; for maintenance of anaesthesia a further bolus of sufentanil (1–2?μg/kg) 10?min before the start of surgery (skin incision) was given. MLAEP were recorded before and 10?min after the last sufentanil bolus on the vertex (positive) and mastoids on both sides (negative). Latencies of the peaks V, Na, Pa, Nb, and P1 (ms) and amplitudes Na/Pa, Pa/Nb, and Nb/P1 (μV) were measured. Results. In the awake state, MLAEP had high peak-to-peak amplitudes and a periodic wave form. During general anaesthesia with sufentanil the brainstem response?V was stable. There was a marked increase in latency and a decrease in the amplitude of Nb and P1. In contrast, for the early cortical potentials Na and Pa only small increases in latencies and decreases in amplitudes were observed. Na and Pa showed a similar pattern to that in awake patients. Conclusions. There is no substantial difference of sufentanil's effect on MLAEP compared with the opioids alfentanil, fentanyl, and morphine. Because Na, Pa, and Nb are generated in the primary auditory cortex of the temporal lobe, it must be concluded that during general anaesthesia with sufentanil primary cortical processing of auditory stimuli may be preserved.     

Midlatency auditory evoked potentials during anaesthesia with increasing endexpiratory concentrations of desflurane

Background. Under general anaesthesia with the volatile anaesthetics halothane, enflurane and isoflurane, midlatency auditory evoked potentials (MLAEP) are suppressed dose-dependently. Therefore, MLAEP have been used to measure depth of anaesthesia and to indicate intraoperative awareness. Desflurane is a new volatile anaesthetic and its effects on MLAEP have not been studied previously.
Methods. We have studied MLAEP during general anaesthesia with increasing endexpiratory concentrations of desflurane in 12 patients scheduled for elective gynaecological surgery. Auditory evoked potentials were recorded in the awake state and during anaesthesia with endexpiratory steady state concentrations of 1.5, 3.0, 4.5 and 6.0 vol %, of desflurane on vertex (positive) and mastoids on both sides (negative). Latencies of the peaks V, Na, Pa, Nb, Pl (ms) and amplitudes Na/Pa, Pa/Nb and Nb/Pl (μV) were measured.
Results. In the awake state, MLAEP had high peak-to-peak amplitudes and a periodic waveform. During general anaesthesia with increasing endexpiratory concentration of desflurane, the latency of the brainstem response V increased only slightly. In contrast, MLAEP showed a marked dose-dependent and statistically significant increase in latencies of Na, Pa, Nb and Pl and decrease in amplitudes of Na/Pa, Pa/Nb and Nb/Pl. Under 6.0 vol % of desflurane MLAEP were severely attenuated or even abolished.
Conclusion. Based on these observations, endexpiratory concentrations of ≥4.5 vol % desflurane should suppress awareness phenomena such as auditory perceptions during anaesthesia.     

Midlatency auditory evoked potentials do not allow the prediction of recovery from general anesthesia with isoflurane

PURPOSE: To investigate midlatency auditory evoked potentials (MLAEP) waveforms during recovery from anesthesia. The hypothesis was that MLAEP are sensitive variables to discriminate between states of consciousness and unconsciousness during emergence from anesthesia. METHODS: MLAEP were recorded in the awake state and during the wake-up phase from isoflurane anesthesia in 22 female patients undergoing ophthalmologic surgery. During emergence from anesthesia the changes in latency and amplitude of MLAEP components Na, Pa and Nb were compared with the awake level. The next day the patients were asked for explicit memory for the recovery period. RESULTS: In 72% of the patients the MLAEP waveforms were completely suppressed during isoflurane anesthesia. When the patients responded and opened their eyes spontaneously 38 +/- 12 min after anesthesia, the latencies of Na (18.3 +/- 1.2 vs 17.6 +/- 1.3; P = 0.013) and Nb (47.4 vs 7.1 vs 44.7 +/- 7.8; P = 0.048) remained prolonged compared with awake values. In contrast, the amplitudes NaPa and PaNb had regained baseline level. Nine patients had explicit memory for the immediate recovery period. However, there was no difference for any MLAEP component between patients with and without memory at any time. CONCLUSIONS: The persistent changes of MLAEP latency components Na and Nb indicated impaired auditory signal processing 38 min after isoflurane anesthesia. There was a marked intra- and inter-individual variability during reversal of the anesthetic induced MLAEP changes. This limits the prediction of recovery of consciousness in the individual patient during emergence from anesthesia.     

异丙酚对大鼠肝BRL-3A细胞缝隙连接功能及顺铂诱导肝BRL-3A细胞毒性的影响

目的 探讨异丙酚对大鼠肝BRL-3A细胞缝隙连接功能及顺铂诱导肝BRL-3A细胞毒性的影响.方法实验Ⅰ:将体外培养的大鼠肝BRL-3A细胞接种于12孔板内,采用随机数字表法,将其随机分为6组(n=8):对照组(C组)、脂肪乳组(10μg/ml,Ⅰ组)、油酸酰胺组(25 μmol/L,O组)和不同浓度异丙酚组[P1组(1.5 μg/ml)、P2组(2.8μg/ml)、P3组(4.1μg/ml)].采用细胞接种荧光示踪法计算荧光示踪剂传递率和抑制率.实验Ⅱ:用不同密度接种方法获得大鼠肝BRL-3A细胞的高密度组(接种密度为1×105个/ml)和低密度组(接种密度为500个/ml),采用随机数字表法,将两组各分为5个亚组(n=8):空白对照亚组;顺铂亚组加入顺铂2.5 μmol/L;顺铂+脂肪乳亚组加入顺铂2.5 μmol/L及脂肪乳10 μg/ml;顺铂+油酸酰胺亚组加入顺铂2.5 μmol/L及油酸酰胺25 μmol/L;顺铂+异丙酚亚组加入顺铂2.5 μmol/L及异丙酚2.8μg/ml,其中油酸酰胺和异丙酚均于顺铂之前加入,单独的作用时间分别为1 h和3 h,与顺铂共同的作用时间为1 h.采用标准细胞集落形成分析法评估异丙酚对顺铂的细胞毒性.结果 与C组比较,O组、P1组、P2组和P3组荧光示踪剂传递率降低,抑制率升高(P＜0.05);异丙酚呈浓度依赖性地降低荧光示踪剂传递率及升高抑制率(P＜0.05).在高密度组中,异丙酚和油酸酰胺可升高细胞集落形成率(P＜0.05),但在低密度组中,未见上述效应(P＞0.05).结论 异丙酚呈浓度依赖性地抑制大鼠肝BRL-3A细胞的缝隙连接功能;异丙酚可减弱顺铂诱导的大鼠肝BRL-3A细胞毒性,其机制可能与抑制细胞缝隙连接功能有关.

Abstract：

Objective To investigate the effect of propofol on the gap junction function of BRL-3A cells and cisplatin-induced toxicity to rat hepatic BRL-3A cells. Methods Rat hepatic BRL-3A cell line was provided by professor Tao laboratory of department of pharmacology of our university and cultured in DMEM liquid culture medium at 37℃. The cells were randomly divided into 6 groups: group Ⅰ control (group C) ; group Ⅱ was exposed to intralipid (the solvent) 10 μg/ml (group Ⅰ) ; group Ⅲ was exposed to oleamide (gap junction function inhibitor) 25 μmol/L (group O) and group Ⅳ ,Ⅴ , Ⅵ were exposed to propofol l.5, 2.8 and 4.1 μg/ml respectively (groups P1, 2,3) . Using "parachute" dye-coupling assay, the dye spread rate and inhibition rate were calculated to measure the gap junction function of BRL-3 A cells. BRL-3 A cells were seeded in two different densities:high density group (seeding density = 1×105 /ml) and low density group (seeding density = 500/ml). Both groups were further divided into 5 subgroups: subgroup Ⅰ control; subgroup Ⅱ was exposed to cisplatin 2.5 μmol/L and subgroup Ⅲ ,Ⅳ ,Ⅴ were exposed to cisplatin 2.5 μmol/L + intralipid 10 μg/ml or oleamide 25 μmol/L or propofol 2.8 μg/ml respectively. The effect of propofol on the cytotoxicity of cisplatin was evaluated by standard colony-forming assay. Results The dye spread rate was significantly lower and inhibition rate higher in groups O,P1 , P2 and P3 than in group C. Propofol decreased the dye spread rate and increased inhibition rate in a concentration-dependent manner. Propofol and oleamide significantly increased colony formation rate in high density group,but had no significant effect on colony formation rate in low density group. Conclusion Propofol can inhibit the gap junction function of BRL-3A cells in a concentration-dependent manner and reduce cisplatin-induced cytotoxicity by inhibiting gap junction function.     

Changes in the Auditory Evoked Potentials and the Bispectral Index following Propofol or Propofol and Alfentanil

Background: Midlatency auditory evoked potentials (MLAEP) show graded changes with increasing doses of hypnotics but little change with opioids. The effect of their combination on the MLAEP was evaluated. Also, the bispectral index (BIS) was compared with the ability of MLAEP to correlate with sedation and predict loss of consciousness.

Methods: Twenty healthy volunteers were randomly assigned to receive stepped increases in propofol concentration (10 subjects) or propofol plus alfentanil 100 ng/ml (10 subjects). At baseline and at each targeted effect site concentration the mean MLAEP, BIS, measures of sedation, and drug concentration were obtained. The relation among MLAEP, BIS, and sedation score was determined. The prediction probability (Pk) was calculated and compared for BIS and MLAEP.

Results: The BIS and MLAEP patterns showed significant changes (Pa and Nb decreased in amplitude and increased in latency) with increasing level of sedation (P < 0.0001). The BIS correlated better with sedation scores (0.884) than did the MLAEP (P < 0.05). Pa and Nb latencies showed the best correlation with sedation levels (0.685 and 0.658, respectively). The addition of alfentanil did not affect the relation between MLAEP and loss of consciousness (P > 0.15). The BIS (Pk = 0.952) was a better predictor of loss of consciousness than were Pa and Nb amplitude (P < 0.05) but were comparable to Pa and Nb latency (Pk = 0.869 and 0.873, respectively).     

Changes in the auditory evoked potentials and the bispectral index following propofol or propofol and alfentanil

BACKGROUND: Midlatency auditory evoked potentials (MLAEP) show graded changes with increasing doses of hypnotics but little change with opioids. The effect of their combination on the MLAEP was evaluated. Also, the bispectral index (BIS) was compared with the ability of MLAEP to correlate with sedation and predict loss of consciousness. METHODS: Twenty healthy volunteers were randomly assigned to receive stepped increases in propofol concentration (10 subjects) or propofol plus alfentanil 100 ng/ml (10 subjects). At baseline and at each targeted effect site concentration the mean MLAEP, BIS, measures of sedation, and drug concentration were obtained. The relation among MLAEP, BIS, and sedation score was determined. The prediction probability (Pk) was calculated and compared for BIS and MLAEP. RESULTS: The BIS and MLAEP patterns showed significant changes (Pa and Nb decreased in amplitude and increased in latency) with increasing level of sedation (P < 0.0001). The BIS correlated better with sedation scores (0.884) than did the MLAEP (P < 0.05). Pa and Nb latencies showed the best correlation with sedation levels (0.685 and 0.658, respectively). The addition of alfentanil did not affect the relation between MLAEP and loss of consciousness (P > 0.15). The BIS (Pk = 0.952) was a better predictor of loss of consciousness than were Pa and Nb amplitude (P < 0.05) but were comparable to Pa and Nb latency (Pk = 0.869 and 0. 873, respectively). CONCLUSION: MLAEP changes, like the BIS, correlate well with increasing sedation produced by propofol, and these changes in the MLAEP are independent of the presence of an opioid. Among all the MLAEP parameters, Pa and Nb latencies are the best predictors of increasing sedation and loss of consciousness.