Effect Of Propofol On Signals Of Otoacoustic Emissions And Spikes Of Inferior Colliculus Neurons

PART ONEEffect of Propofol at Different Effect-Site Concentration on Signals of Otoacoustice Missions of AdultOBJECTIVETo 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.METHODSThirty 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.RESULSIt 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.CONCLUSIONThere 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 TWOEffect of Propofol on Spikes of rat Inferior Colliculus NeuronsOBJECTIVETo evaluate effect of propofol on spikes of rat inferior colliculus neurons and to findout neurophysiological mechanism of propofol on neurons in inferior colliculus. METHODSFifteen 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.RESULSData 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 anesthesiaResponse 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).CONCLUSIONPropofol 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 inhibitionTO SUMMARIZEThe 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.