丙泊酚对耳声发射及下丘神经元放电的影响
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摘要
第一部分丙泊酚不同效应室浓度对人耳声发射的影响
目的
研究丙泊酚不同效应室浓度对人畸变产物耳声发射(DPOAE)检出率、幅值及信噪比的影响;丙泊酚不同效应室浓度对人瞬态诱发耳声发射(TEOAE)总反应幅值、总重复率、各频带相应反应幅值、信噪比以及TEOAE信号近似熵(ApEn)的影响,以探讨丙泊酚对耳蜗功能的作用。
方法
拟气管插管全麻下行胸部以下的择期手术患者30例,ASAⅠ或Ⅱ级,年龄18～49岁,体重指数(BMI)18.5～25(kg/m2)。听力正常且无先天性耳聋家族史、无近期耳毒性药物应用史、无长期噪声接触史、否认有耳鸣、耳聋、眩晕史。受试前均经耳镜检查,外耳道、鼓膜正常。纯音听阈测试(MadsenMM633)语言频率(0.5、1、2kHz),平均听阈在15dBSPL以内。声导抗(MadsenZ0901)鼓室导抗图均为“A”型、声反射均正常。15例研究DPOAE,15例研究TEOAE。
DPOAE
麻醉诱导期丙泊酚靶控输注的效应室浓度依次设定为1μg/ml、2μg/ml、3μg/ml、4μg/ml,不同效应室浓度代表不同麻醉深度。SmartOAE耳声发射检测仪记录诱导前及诱导过程中不同麻醉深度各频率点(0.5KHz、0.7Kttz、1KHz、1.4KHz、2KHz、3KHz、4KHz、6KHz、8KHz)DPOAE的幅值及信噪比,并记录相同麻醉深度DPOAE的所有频点检出率。采用自身对照,研究不同麻醉深度下各频率点DPOAE幅值、信噪比及检出率的变化。
TEOAE
麻醉方法同DPOAE的研究。Smart0Ag耳声发射检测仪以声强80dB SPL持续时间80μs的短声作为刺激声,并记录诱导前及诱导过程中不同麻醉深度TEOAE总反应幅值、总重复率及各频带(1KHz、1.5KHz、2KHz、3KHz、4KHz)相应TEOAE的反应幅值、信噪比。采用自身对照,研究不同麻醉深度下各频带TEOAE相关参数的变化。
TEOAE的ApEn
数据来源与TEOAE波形数据。数据经MATLAB软件处理,将其分为四段分别对应频带0～2kHz、1～3kHz、2.5～4.5kHz、4～6kHz,求出其相应的ApEn后应用SPSS13.0软件进行统计学分析,比较不同效应室浓度下ApEn的变化。
结果
诱导前与诱导过程中不同麻醉深度各频率点DPOAE幅值反应稳定,在麻醉状态下检出率高于诱导前(χ~2=19.37,P=0.000,n=135),但不同麻醉深度检出率没有显著差别(χ~2=3.662,P=0.300);丙泊酚不同麻醉深度对人DPOAE幅值及信噪比的改变无统计学意义(F=0.954,P=0.440;F=0.620,P=0.950)。
诱导前与诱导过程中不同麻醉深度总反应幅值、总重复率及各频带TEOAE幅值反应稳定,但不同麻醉深度总反应幅值、总重复率及各测试频带反应幅值及信噪比的变化没有显著性差别(F=0.297,P=0.879;F=0.327,P=0.859;F=0.395,P=0.811;F=0.693,P=0.600)。
相同频段TEOAE信号的ApEn在不同效应室浓度下比较没有统计学意义(F=1.121,P=0.356)。同效应室浓度TEOAE信号的ApEn在不同频段差别无统计学意义(F=1.412,P=0.241)。
结论
丙泊酚不同效应室浓度对人畸变产物耳声发射、瞬态诱发耳声发射以及瞬态诱发耳声发射信号近似熵的影响不显著,丙泊酚常规剂量对耳蜗功能影响不大。对患者适当镇静可提高畸变产物耳声发射的检出率。
第二部分丙泊酚对大鼠下丘神经元的作用
目的
研究丙泊酚对大鼠下丘单单位神经元放电的作用方式,以探讨丙泊酚对大鼠听觉神经元作用的神经生理机制。
方法
雌雄不拘SD大鼠15只,体质量200-250g。清醒动物模型插管并机械通气后固定于立体定位仪后,通过微操纵仪推进微记录电极插入下丘。给予50ms的噪音刺激(duration,50ms;rise time,5ms;fall time,5ms。Duration不包括risetime和fall time)探测动物神经元的反应,探测到后再换为相应特征频率(CF)的纯音刺激。数据通过TDT3系统来获取并分析。神经元反应一般放大2000至10000倍,采用数字放大器(RA16)进行滤波(0.3—3kHz),通过BrainWare软件进行记录和显示,同时通过音频监听器(MS2)来进行监听。对信噪比大于4:1的反应的动作电位进行进一步分析,并在数据获取过程中进行观察,探查到神经元反应后,将声音刺激换为纯音,首先通过改变短纯音的频率和幅度来大致确定其特征频率和最小阈值(MT)。为研究清醒与麻醉不同时间点变化及能够得到相对精确的CF和MT,改变纯音刺激参数(duration,50ms;rise time,20ms;fall time,10ms。Duration不包括rise time和fall time)进行频率—幅度(F-A)扫描,声音频率在CF±5kHz范围内以1或0.5kHz为一个单位变化,同时幅度从90dB SPL至阈下10dB(MT—10dB),以5-20dB SPL为单位变化,而当幅度接近阈值时以1-3dB SPL为间隔进行变化。每个声音刺激通过BrainWare软件以每秒一次(1Hz)的速度随机发出,每个参数相同的刺激都重复10～15次。应用同一刺激参数分别于麻醉前、腹腔注射丙泊酚10分钟以及麻醉后不同时间点进行扫描。研究参数包括:自发放(SA)、发放数(SC)、CF及其MT、反应类型、第一个动作电位潜伏期(First spike latency,FSL)。数据用BrainWare软件通过发放数顺序,刺激后时间直方图(Post-stimums timehistograms,PSTH),动作电位形状和特征窗进行观察。声音刺激下诱发的动作电位的波形,数目和时间都被收集并存储在数据库中。
结果
实验共记录到43个单单位神经元,所有神经元对短纯音反应CF范围在2.5～44kHz之间(12.06±8.77kHz)。记录电极垂直向后插入大鼠脑组织到达下丘的深度在1865～4537μm之间(3435.65±651.00μm)。神经元的CF和记录电极深度有明显的正相关(r=0.581,P＜0.000),记录电极越深CF越高。
本实验记录到1个单单位神经元呈现Offset反应(NO.080118),麻醉前、麻醉后FSL分别为:83.597ms、84.4335ms,麻醉后FSL延长0.8365ms(90dB SPL,频率=CF)。丙泊酚对该神经元反应特性表现延时增加。其余42个单单神经元清醒状态时FSL为:13.35122±3.329865ms(8.681571～22.02218ms),麻醉后10分钟FSL为:14.10955±3.392343ms(8.998～21.84244ms),麻醉前、后FSL差异性有统计学意义(t=-4.558,P=0.000)。其中36个单单位神经元(83.7%)麻醉后表现FSL增加(0.969981±1.071691ms);7个单单位神经元(16.3%)麻醉后表现FSL缩短(0.31896±0.222143ms)。麻醉前后声强延时指数函数拟合曲线上下或左右移动基本完全重合。
麻醉后10个神经元(33.3%)发生放电模式的改变,其中1个神经元放电模式向发放数增多的类型改变,其余9个神经元放电模式则向发放数减少类型改变。
记录到43个神经元中30个可以明确其最小阈值(Minimum threshold,MT)。神经元清醒和麻醉状态下MT分别在5～68、5～74dB SPL之间。麻醉后MT显著升高,与清醒状态比较,差别有统计学意义(t=-6.598,P=0.000)。麻醉后与清醒状态比较1个神经元(3.3%)MT降低,2个神经元(6.7%)MT没有变化,其余27个(90%)均升高,感受野减小。
记录到43个单单位神经元中1个神经元麻醉后发放数增加,7个神经元放电模式为相位型无法比较麻醉前、后发放数,其余35个神经元均在麻醉后发放数减少。以NO.080610神经元为例进行统计学分析,随着麻醉深度的不同发放数也有所不同(χ~2=375.679,P=0.000)。19个神经元(44%)显示自发放电,麻醉后自发放电的神经元数量减少至12个(28%),麻醉前后差别有统计学意义(χ~2=8.977,P=0.030)。
结论
丙泊酚使下丘神经元第一动作电位潜伏期、固定延时增加,发放数、自发放数减少,阈值提高,神经元放电模式发生改变。丙泊酚使听觉中枢下丘神经元的兴奋性降低是麻醉影响听觉信息传递的重要因素之一。
PART ONE
Effect of Propofol at Different Effect-Site Concentration on Signals of Otoacoustice Missions of Adult
OBJECTIVE
To study effect of propofol under dfiferent effect-site concentration on evoked otoacoustice missions(OAE) signals of adult and to findout whether anesthesia affect cochlear function.
METHODS
Thirty ASAⅠorⅡpatients aged 18～49 yrs undergoing operation below cervical part under general anaesthesia were enrolled in this study.Patients with aural disease were excluded and no patients were taking any drugs that might influence OAE signals.Anesthesia was maintained with propofol by TCI(target-controlled infusion),the effect-site concentration was set at 1μg/ml,2μg/ml,3μ/ml,4μg/ml respectively.Distortion product otoacoustic emissions(DPOAE;fifteen patients) or transient evoked otoacoustice missions(TEOAE;fifteen patients) signals was monitored and recorded by SmartOAE(3.X,HIS,USA)before and after anesthesia.
DPOAE signals were monitored and recorded then compared incidence, response amplitude and band signal tonoise ratio(SNR) at different frequency(0.5KHz、0.7 KHz、1 KHz、1.4 KHz、2 KHz、3 KHz、4 KHz、6 KHz、8 KHz).
TEOAE signals were monitored and recorded response amplitude,wave reproducibility,Band(1KHz、1.5 KHz、2 KHz、3 KHz、4 KHz) response amplitude, SNR.then compared them.
Approximate entropy(ApEn) of TEOAE were calculated using MATLAB software according to the data recorded before which were divided into four frequency paragraphs that were from 0 kHz to 2 kHz,from 1 to 3 kHz,from 2.5 to 4.5 kHz and from 4 to 6 kHz.
Incidence of DPOAE was analysed with Chi-Square Test.All the other data was analysed with repeadted measures.SPSS 13.0 statistical software was used.
RESULS
It was significant difference for the incidence of DPOAE at different effect-site concentration of propofol((X~2=19.37,P=0.000,n=135,Chi-Square Test).It was not significant difference for the incidence of DPOAE after anesthesia(Chi-Square Test,X~2 =3.662,P=0.300,n=135).It was not significant difference for amplitude and SNR of DPOAE at different effect-site concentration of propofol(F=0.954,P =0.440;F=0.620,P=0.950.repeadted measures).
It was not significant for response amplitude,wave reproducibility,Band response amplitude,Band SNR under different effect-site concentration of propofol (F=0.297,P=0.879;F=0.327,P=0.859;F=0.395,P=0.811;F=0.693, P=0.600.repeadted measures).
It was not significant for the ApEn of the different frequency paragraph under the same effect-site concentration of propofol and the different effect-site concentration under the same frequency paragraph(F=1.121,P=0.356.repeadted measures).
All statistical tests were performed using SPSS 13.0 software(SPSS Inc.,Chicago, Illinois,USA).The incidence of DPOAE was test by Chi-Square Test.Repeated measures was applied to test the difference for the others.Reported P values were corrected.
CONCLUSION
There is no effect of propofol on signals of OAE of adult at different effect-site concentration.It is useful for improving the incidence of DPOAE to sedate properly. Propofol did not affect cochlear function under general anesthesia.
PART TWO
Effect of Propofol on Spikes of rat Inferior Colliculus Neurons
OBJECTIVE
To evaluate effect of propofol on spikes of rat inferior colliculus neurons and to findout neurophysiological mechanism of propofol on neurons in inferior colliculus.
METHODS
Fifteen healthy female rat(aged 1-2 months,weighing 200-250 g),without any hearing defects,were first injected subcutaneously with atropine sulfate(0.2 mg/kg) ventilated(V_T=5～10ml,RR=75～110bpm) after infusing vecuronium.The animal's head was rigidly held in a stereotaxic apparatus by a special holder,fixed to the skull by two screws and secured by acrylic resin.This type of fixation enabled the animal's head to be free for electrode penetration and for free-field acoustical stimulation.A rectal temperature of 37-38℃was maintained by a heating pad.Pure tone bursts were used as acoustic stimuli and were generated and delivered using a Tucker-Davis Technologies System 3(TDT 3,Tucker-Davis Technologies,Alachua, FL,USA).First,a series of digital tone burst signals lasting 50 ms each with a 5 ms rise-fall time were synthesized using a real-time processor(RP 2.1) and a custommade program written with RPvdsEx software and inputted into a program mable attenuator(PA5).The synthesized signals were amplified by an electrostatic speaker driver(ED1) and delivered to the mouse via a free-field ultrasonic loudspeaker(ES1, frequency range 2-110 kHz),located at 30 cm from the front of the animal's head. Pure tone bursts were played,back using a computer with BrainWare software which controlled the frequency and amplitude of pure tone bursts either manually or automatically,via the RP2.1 and PA5.
Extracellular recordings were made with glass micropipettes filled with 2 M sodium acetate,and data were acquired and processed online with TDT 3.The neuronal signals were amplified 2000 - 10,000 times,filtered by a band-pass of 0.3 -3 kHz with a digital amplifier RA16,and were,in turn,recorded and displayed with BrainWare software.During penetration of a microelectrode in the IC with a microdriver,neuronal responses were detected by presenting 50 ms noise bursts to the animal.Single units responding to pure tones were then isolated by clustering small feature space.The shape and feature space of action potentials were stored and monitored during data acquisition.The recorded action potentials were selected for further analysis only when the signal-noise ratio was greater than 4:1.The CF and minimum threshold(MT) were first measured approximately by manually varying the frequency and amplitude of tone bursts after an IC neuron was isolated.A frequency and amplitude(F-A) scan was then performed in which frequencies were varied in the range,CF±5 kHz,in 1 or 0.5 kHz steps.The amplitudes of acoustic stimuli were simultaneously varied from 90 dB SPL to 10 dB lower than MT in 5-20 dB steps or in 1-3 dB steps when the amplitude was close to MT.To obtain data sets,each sound was presented randomly with the parameters as described above at a rate of 1/s using BrainWare.Each identical scan was repeated 10～15 times.The waveforms,numbers and timings of spikes evoked by acoustic stimuli were collected and stored as data sets.The data were monitored with respect to SC-level,frequency function, post-stimulus time histograms(PSTH),spike shapes and feature space window using BrainWare.The following parameters of the response were evaluated:The level of the spontaneous firing rate,The threshold of responses at the CF,The type of response,The first-spike latency,Rate/level functions.The animal was anesthetized with propofol(100 mg/kg i.p.) and then the parameters were recorded repeatly after 10 minutes.
All statistical tests were performed using SPSS13.0 software for each and all administrated neuron(s).The significance of differences between individual sets of experimental data was tested by t-test,Tukey test,repeated measures analysis of variance or chi-square test.Reported P values were corrected.
RESULS
Data were collected at depths between 1865 and 4537μm in ICs and were derived from a total of 43 well-isolated single neurons with CFs ranging from 2.5 to 44 kHz.CF values was positively correlated with the depth(r=0.581,P<0.000).One offset response neuron was record.FSL was 13.35122±3.329865 ms(8.681571～22.02218 ms)and 14.10955±3.392343ms(8.998-21.84244ms)in awake and anesthesia respectively(t=-4.558,P=0.000;Paired-Samples T Test).FSL was longer in anesthesia than that in awake except seven neurons(16.3%) whose FSL shortened about 0.31896ms.FSL-intensity curves fitted by exponential growth were in polymerization in awake and anesthesia.
The temporal discharge patterns of IC neurons were classified into four basic categories on the basis of their PSTH shape.Nine neurons discharge patterns (21.4%)changed from sustained response type to onset or others which discharge rate reduced after anesthesia
Response thresholds of thirty neurons were assessed by decreasing the stimulus intensity in 5 dB and 1 dB steps.Most of them(27,90%) increased.It was significant difference for MT value in awake and anesthesia(t=-6.598,P =0.000;Paired-Samples T Test).
Spike counts of thirty-five neurons reduced after anesthesia except seven neurons that can not compare.It was significant difference for Mean Rank value in awake and anesthesia(X~2=375.679,P=0.000;Friedman Test).
Nnumber of neurons with spontaneous activity reduced after anesthesia.It was significant difference for the incidence of neurons with spontaneous activity in awake and anaesthasia(X~2=8.977,P=0.030,chi-Square Test).
CONCLUSION
Propofol prolongded FSL of rat inferior colliculus Neurons,increased response thresholds,changed discharge patterns,reduced spike counts and spontaneous active neurons.The effect of propofol involves the processing of acoustical information at inferior colliculus.The observed changes are consistent with an overall enhancement of inhibition
TO SUMMARIZE
The first:
There is no effect of propofol on signals of OAE of adult at different effect-site concentration.It is useful for improving the incidence of DPOAE to sedate properly. Propofol did not affect cochlear function under general anesthesia.
The second:
Propofol prolongded FSL of rat inferior colliculus Neurons,increased response thresholds,changed discharge patterns,reduced spike counts and spontaneous active neurons.The observed changes are consistent with an overall enhancement of inhibition.The effect of propofol involves the processing of acoustical information at inferior colliculus.
目的
研究丙泊酚不同效应室浓度对人畸变产物耳声发射(DPOAE)检出率、幅值及信噪比的影响;丙泊酚不同效应室浓度对人瞬态诱发耳声发射(TEOAE)总反应幅值、总重复率、各频带相应反应幅值、信噪比以及TEOAE信号近似熵(ApEn)的影响,以探讨丙泊酚对耳蜗功能的作用。
方法
拟气管插管全麻下行胸部以下的择期手术患者30例,ASAⅠ或Ⅱ级,年龄18～49岁,体重指数(BMI)18.5～25(kg/m2)。听力正常且无先天性耳聋家族史、无近期耳毒性药物应用史、无长期噪声接触史、否认有耳鸣、耳聋、眩晕史。受试前均经耳镜检查,外耳道、鼓膜正常。纯音听阈测试(MadsenMM633)语言频率(0.5、1、2kHz),平均听阈在15dBSPL以内。声导抗(MadsenZ0901)鼓室导抗图均为“A”型、声反射均正常。15例研究DPOAE,15例研究TEOAE。
DPOAE
麻醉诱导期丙泊酚靶控输注的效应室浓度依次设定为1μg/ml、2μg/ml、3μg/ml、4μg/ml,不同效应室浓度代表不同麻醉深度。SmartOAE耳声发射检测仪记录诱导前及诱导过程中不同麻醉深度各频率点(0.5KHz、0.7Kttz、1KHz、1.4KHz、2KHz、3KHz、4KHz、6KHz、8KHz)DPOAE的幅值及信噪比,并记录相同麻醉深度DPOAE的所有频点检出率。采用自身对照,研究不同麻醉深度下各频率点DPOAE幅值、信噪比及检出率的变化。
TEOAE
麻醉方法同DPOAE的研究。Smart0Ag耳声发射检测仪以声强80dB SPL持续时间80μs的短声作为刺激声,并记录诱导前及诱导过程中不同麻醉深度TEOAE总反应幅值、总重复率及各频带(1KHz、1.5KHz、2KHz、3KHz、4KHz)相应TEOAE的反应幅值、信噪比。采用自身对照,研究不同麻醉深度下各频带TEOAE相关参数的变化。
TEOAE的ApEn
数据来源与TEOAE波形数据。数据经MATLAB软件处理,将其分为四段分别对应频带0～2kHz、1～3kHz、2.5～4.5kHz、4～6kHz,求出其相应的ApEn后应用SPSS13.0软件进行统计学分析,比较不同效应室浓度下ApEn的变化。
结果
诱导前与诱导过程中不同麻醉深度各频率点DPOAE幅值反应稳定,在麻醉状态下检出率高于诱导前(χ~2=19.37,P=0.000,n=135),但不同麻醉深度检出率没有显著差别(χ~2=3.662,P=0.300);丙泊酚不同麻醉深度对人DPOAE幅值及信噪比的改变无统计学意义(F=0.954,P=0.440;F=0.620,P=0.950)。
诱导前与诱导过程中不同麻醉深度总反应幅值、总重复率及各频带TEOAE幅值反应稳定,但不同麻醉深度总反应幅值、总重复率及各测试频带反应幅值及信噪比的变化没有显著性差别(F=0.297,P=0.879;F=0.327,P=0.859;F=0.395,P=0.811;F=0.693,P=0.600)。
相同频段TEOAE信号的ApEn在不同效应室浓度下比较没有统计学意义(F=1.121,P=0.356)。同效应室浓度TEOAE信号的ApEn在不同频段差别无统计学意义(F=1.412,P=0.241)。
结论
丙泊酚不同效应室浓度对人畸变产物耳声发射、瞬态诱发耳声发射以及瞬态诱发耳声发射信号近似熵的影响不显著,丙泊酚常规剂量对耳蜗功能影响不大。对患者适当镇静可提高畸变产物耳声发射的检出率。
第二部分丙泊酚对大鼠下丘神经元的作用
目的
研究丙泊酚对大鼠下丘单单位神经元放电的作用方式,以探讨丙泊酚对大鼠听觉神经元作用的神经生理机制。
方法
雌雄不拘SD大鼠15只,体质量200-250g。清醒动物模型插管并机械通气后固定于立体定位仪后,通过微操纵仪推进微记录电极插入下丘。给予50ms的噪音刺激(duration,50ms;rise time,5ms;fall time,5ms。Duration不包括risetime和fall time)探测动物神经元的反应,探测到后再换为相应特征频率(CF)的纯音刺激。数据通过TDT3系统来获取并分析。神经元反应一般放大2000至10000倍,采用数字放大器(RA16)进行滤波(0.3—3kHz),通过BrainWare软件进行记录和显示,同时通过音频监听器(MS2)来进行监听。对信噪比大于4:1的反应的动作电位进行进一步分析,并在数据获取过程中进行观察,探查到神经元反应后,将声音刺激换为纯音,首先通过改变短纯音的频率和幅度来大致确定其特征频率和最小阈值(MT)。为研究清醒与麻醉不同时间点变化及能够得到相对精确的CF和MT,改变纯音刺激参数(duration,50ms;rise time,20ms;fall time,10ms。Duration不包括rise time和fall time)进行频率—幅度(F-A)扫描,声音频率在CF±5kHz范围内以1或0.5kHz为一个单位变化,同时幅度从90dB SPL至阈下10dB(MT—10dB),以5-20dB SPL为单位变化,而当幅度接近阈值时以1-3dB SPL为间隔进行变化。每个声音刺激通过BrainWare软件以每秒一次(1Hz)的速度随机发出,每个参数相同的刺激都重复10～15次。应用同一刺激参数分别于麻醉前、腹腔注射丙泊酚10分钟以及麻醉后不同时间点进行扫描。研究参数包括:自发放(SA)、发放数(SC)、CF及其MT、反应类型、第一个动作电位潜伏期(First spike latency,FSL)。数据用BrainWare软件通过发放数顺序,刺激后时间直方图(Post-stimums timehistograms,PSTH),动作电位形状和特征窗进行观察。声音刺激下诱发的动作电位的波形,数目和时间都被收集并存储在数据库中。
结果
实验共记录到43个单单位神经元,所有神经元对短纯音反应CF范围在2.5～44kHz之间(12.06±8.77kHz)。记录电极垂直向后插入大鼠脑组织到达下丘的深度在1865～4537μm之间(3435.65±651.00μm)。神经元的CF和记录电极深度有明显的正相关(r=0.581,P＜0.000),记录电极越深CF越高。
本实验记录到1个单单位神经元呈现Offset反应(NO.080118),麻醉前、麻醉后FSL分别为:83.597ms、84.4335ms,麻醉后FSL延长0.8365ms(90dB SPL,频率=CF)。丙泊酚对该神经元反应特性表现延时增加。其余42个单单神经元清醒状态时FSL为:13.35122±3.329865ms(8.681571～22.02218ms),麻醉后10分钟FSL为:14.10955±3.392343ms(8.998～21.84244ms),麻醉前、后FSL差异性有统计学意义(t=-4.558,P=0.000)。其中36个单单位神经元(83.7%)麻醉后表现FSL增加(0.969981±1.071691ms);7个单单位神经元(16.3%)麻醉后表现FSL缩短(0.31896±0.222143ms)。麻醉前后声强延时指数函数拟合曲线上下或左右移动基本完全重合。
麻醉后10个神经元(33.3%)发生放电模式的改变,其中1个神经元放电模式向发放数增多的类型改变,其余9个神经元放电模式则向发放数减少类型改变。
记录到43个神经元中30个可以明确其最小阈值(Minimum threshold,MT)。神经元清醒和麻醉状态下MT分别在5～68、5～74dB SPL之间。麻醉后MT显著升高,与清醒状态比较,差别有统计学意义(t=-6.598,P=0.000)。麻醉后与清醒状态比较1个神经元(3.3%)MT降低,2个神经元(6.7%)MT没有变化,其余27个(90%)均升高,感受野减小。
记录到43个单单位神经元中1个神经元麻醉后发放数增加,7个神经元放电模式为相位型无法比较麻醉前、后发放数,其余35个神经元均在麻醉后发放数减少。以NO.080610神经元为例进行统计学分析,随着麻醉深度的不同发放数也有所不同(χ~2=375.679,P=0.000)。19个神经元(44%)显示自发放电,麻醉后自发放电的神经元数量减少至12个(28%),麻醉前后差别有统计学意义(χ~2=8.977,P=0.030)。
结论
丙泊酚使下丘神经元第一动作电位潜伏期、固定延时增加,发放数、自发放数减少,阈值提高,神经元放电模式发生改变。丙泊酚使听觉中枢下丘神经元的兴奋性降低是麻醉影响听觉信息传递的重要因素之一。
PART ONE
Effect of Propofol at Different Effect-Site Concentration on Signals of Otoacoustice Missions of Adult
OBJECTIVE
To study effect of propofol under dfiferent effect-site concentration on evoked otoacoustice missions(OAE) signals of adult and to findout whether anesthesia affect cochlear function.
METHODS
Thirty ASAⅠorⅡpatients aged 18～49 yrs undergoing operation below cervical part under general anaesthesia were enrolled in this study.Patients with aural disease were excluded and no patients were taking any drugs that might influence OAE signals.Anesthesia was maintained with propofol by TCI(target-controlled infusion),the effect-site concentration was set at 1μg/ml,2μg/ml,3μ/ml,4μg/ml respectively.Distortion product otoacoustic emissions(DPOAE;fifteen patients) or transient evoked otoacoustice missions(TEOAE;fifteen patients) signals was monitored and recorded by SmartOAE(3.X,HIS,USA)before and after anesthesia.
DPOAE signals were monitored and recorded then compared incidence, response amplitude and band signal tonoise ratio(SNR) at different frequency(0.5KHz、0.7 KHz、1 KHz、1.4 KHz、2 KHz、3 KHz、4 KHz、6 KHz、8 KHz).
TEOAE signals were monitored and recorded response amplitude,wave reproducibility,Band(1KHz、1.5 KHz、2 KHz、3 KHz、4 KHz) response amplitude, SNR.then compared them.
Approximate entropy(ApEn) of TEOAE were calculated using MATLAB software according to the data recorded before which were divided into four frequency paragraphs that were from 0 kHz to 2 kHz,from 1 to 3 kHz,from 2.5 to 4.5 kHz and from 4 to 6 kHz.
Incidence of DPOAE was analysed with Chi-Square Test.All the other data was analysed with repeadted measures.SPSS 13.0 statistical software was used.
RESULS
It was significant difference for the incidence of DPOAE at different effect-site concentration of propofol((X~2=19.37,P=0.000,n=135,Chi-Square Test).It was not significant difference for the incidence of DPOAE after anesthesia(Chi-Square Test,X~2 =3.662,P=0.300,n=135).It was not significant difference for amplitude and SNR of DPOAE at different effect-site concentration of propofol(F=0.954,P =0.440;F=0.620,P=0.950.repeadted measures).
It was not significant for response amplitude,wave reproducibility,Band response amplitude,Band SNR under different effect-site concentration of propofol (F=0.297,P=0.879;F=0.327,P=0.859;F=0.395,P=0.811;F=0.693, P=0.600.repeadted measures).
It was not significant for the ApEn of the different frequency paragraph under the same effect-site concentration of propofol and the different effect-site concentration under the same frequency paragraph(F=1.121,P=0.356.repeadted measures).
All statistical tests were performed using SPSS 13.0 software(SPSS Inc.,Chicago, Illinois,USA).The incidence of DPOAE was test by Chi-Square Test.Repeated measures was applied to test the difference for the others.Reported P values were corrected.
CONCLUSION
There is no effect of propofol on signals of OAE of adult at different effect-site concentration.It is useful for improving the incidence of DPOAE to sedate properly. Propofol did not affect cochlear function under general anesthesia.
PART TWO
Effect of Propofol on Spikes of rat Inferior Colliculus Neurons
OBJECTIVE
To evaluate effect of propofol on spikes of rat inferior colliculus neurons and to findout neurophysiological mechanism of propofol on neurons in inferior colliculus.
METHODS
Fifteen healthy female rat(aged 1-2 months,weighing 200-250 g),without any hearing defects,were first injected subcutaneously with atropine sulfate(0.2 mg/kg) ventilated(V_T=5～10ml,RR=75～110bpm) after infusing vecuronium.The animal's head was rigidly held in a stereotaxic apparatus by a special holder,fixed to the skull by two screws and secured by acrylic resin.This type of fixation enabled the animal's head to be free for electrode penetration and for free-field acoustical stimulation.A rectal temperature of 37-38℃was maintained by a heating pad.Pure tone bursts were used as acoustic stimuli and were generated and delivered using a Tucker-Davis Technologies System 3(TDT 3,Tucker-Davis Technologies,Alachua, FL,USA).First,a series of digital tone burst signals lasting 50 ms each with a 5 ms rise-fall time were synthesized using a real-time processor(RP 2.1) and a custommade program written with RPvdsEx software and inputted into a program mable attenuator(PA5).The synthesized signals were amplified by an electrostatic speaker driver(ED1) and delivered to the mouse via a free-field ultrasonic loudspeaker(ES1, frequency range 2-110 kHz),located at 30 cm from the front of the animal's head. Pure tone bursts were played,back using a computer with BrainWare software which controlled the frequency and amplitude of pure tone bursts either manually or automatically,via the RP2.1 and PA5.
Extracellular recordings were made with glass micropipettes filled with 2 M sodium acetate,and data were acquired and processed online with TDT 3.The neuronal signals were amplified 2000 - 10,000 times,filtered by a band-pass of 0.3 -3 kHz with a digital amplifier RA16,and were,in turn,recorded and displayed with BrainWare software.During penetration of a microelectrode in the IC with a microdriver,neuronal responses were detected by presenting 50 ms noise bursts to the animal.Single units responding to pure tones were then isolated by clustering small feature space.The shape and feature space of action potentials were stored and monitored during data acquisition.The recorded action potentials were selected for further analysis only when the signal-noise ratio was greater than 4:1.The CF and minimum threshold(MT) were first measured approximately by manually varying the frequency and amplitude of tone bursts after an IC neuron was isolated.A frequency and amplitude(F-A) scan was then performed in which frequencies were varied in the range,CF±5 kHz,in 1 or 0.5 kHz steps.The amplitudes of acoustic stimuli were simultaneously varied from 90 dB SPL to 10 dB lower than MT in 5-20 dB steps or in 1-3 dB steps when the amplitude was close to MT.To obtain data sets,each sound was presented randomly with the parameters as described above at a rate of 1/s using BrainWare.Each identical scan was repeated 10～15 times.The waveforms,numbers and timings of spikes evoked by acoustic stimuli were collected and stored as data sets.The data were monitored with respect to SC-level,frequency function, post-stimulus time histograms(PSTH),spike shapes and feature space window using BrainWare.The following parameters of the response were evaluated:The level of the spontaneous firing rate,The threshold of responses at the CF,The type of response,The first-spike latency,Rate/level functions.The animal was anesthetized with propofol(100 mg/kg i.p.) and then the parameters were recorded repeatly after 10 minutes.
All statistical tests were performed using SPSS13.0 software for each and all administrated neuron(s).The significance of differences between individual sets of experimental data was tested by t-test,Tukey test,repeated measures analysis of variance or chi-square test.Reported P values were corrected.
RESULS
Data were collected at depths between 1865 and 4537μm in ICs and were derived from a total of 43 well-isolated single neurons with CFs ranging from 2.5 to 44 kHz.CF values was positively correlated with the depth(r=0.581,P<0.000).One offset response neuron was record.FSL was 13.35122±3.329865 ms(8.681571～22.02218 ms)and 14.10955±3.392343ms(8.998-21.84244ms)in awake and anesthesia respectively(t=-4.558,P=0.000;Paired-Samples T Test).FSL was longer in anesthesia than that in awake except seven neurons(16.3%) whose FSL shortened about 0.31896ms.FSL-intensity curves fitted by exponential growth were in polymerization in awake and anesthesia.
The temporal discharge patterns of IC neurons were classified into four basic categories on the basis of their PSTH shape.Nine neurons discharge patterns (21.4%)changed from sustained response type to onset or others which discharge rate reduced after anesthesia
Response thresholds of thirty neurons were assessed by decreasing the stimulus intensity in 5 dB and 1 dB steps.Most of them(27,90%) increased.It was significant difference for MT value in awake and anesthesia(t=-6.598,P =0.000;Paired-Samples T Test).
Spike counts of thirty-five neurons reduced after anesthesia except seven neurons that can not compare.It was significant difference for Mean Rank value in awake and anesthesia(X~2=375.679,P=0.000;Friedman Test).
Nnumber of neurons with spontaneous activity reduced after anesthesia.It was significant difference for the incidence of neurons with spontaneous activity in awake and anaesthasia(X~2=8.977,P=0.030,chi-Square Test).
CONCLUSION
Propofol prolongded FSL of rat inferior colliculus Neurons,increased response thresholds,changed discharge patterns,reduced spike counts and spontaneous active neurons.The effect of propofol involves the processing of acoustical information at inferior colliculus.The observed changes are consistent with an overall enhancement of inhibition
TO SUMMARIZE
The first:
There is no effect of propofol on signals of OAE of adult at different effect-site concentration.It is useful for improving the incidence of DPOAE to sedate properly. Propofol did not affect cochlear function under general anesthesia.
The second:
Propofol prolongded FSL of rat inferior colliculus Neurons,increased response thresholds,changed discharge patterns,reduced spike counts and spontaneous active neurons.The observed changes are consistent with an overall enhancement of inhibition.The effect of propofol involves the processing of acoustical information at inferior colliculus.
引文
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