生物医学电子学乔清理课件

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单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,生物医学电子学,2013,2014,学年第二学期,2013,09,04,生物医学电子学 20132014学年第二学期,1,引言,可兴奋细胞与生物电位,生物电位研究与测量的意义,生物电与人工电的区别,静息电位,细胞膜,泵与通道,Nernst,电位,静息电位,动作电位,action potentials recording,breakdown,”,hypothesis,钠离子学说,Hodgkin,和,Huxley,的其它贡献,无髓神经传播的动作电位,有髓神经传播的动作电位,Ch2 The Origin of Biopotentials, Noise and interference,引言Ch2 The Origin of Biopotenti,2,Volume conductor field,生物电容积源和容积导体的概念,描述生物容积电源和容积导体中场的量,生物容积电源的基本模型及其场,单根神经(,Single Fiber,)的等价电流源极其场,神经干(,Nerve trunk,)的胞外电场,心脏的兴奋与传导系统,心肌细胞动作电位,心肌细胞间的连接,心室激活,心向量,体表电位,导联向量,标准导联(,Eindhvon Triangle,),单极导联,参考电极,Wilson central terminal,增强导联与胸导联,,12,导联,Volume conductor field,3,Bioelectric potentials are produced as a results of electrochemical activity of a certain class of excitable cells,These cells are components of nervous, muscular,and glandular tissue.,The excitable cells,a,Resting potential or Action potential (when approciately stimulated),可兴奋性细胞,Bioelectric potentials are pro,4,可兴奋性细胞,(,Excitable cells,),可兴奋性细胞:能够产生电流和电位的细胞。包括 神经细胞和肌肉纤维(骨骼肌细胞、心肌细胞)和感受器细胞。,描述电行为的量: 电位和电流,,分布: 细胞内、细胞膜、细胞膜外与体表之间,,作用: 传输信号,控制肌肉,(听,视)感觉输 入, 内脏等各个生理过程,可兴奋性细胞(Excitable cells),5,生物电与人工电的区别,:,历史观点,:,由,Luigi Galvanin,在,1780s,发现,称为,“animal electricity”,,是一种由大脑产生的特殊液体,通过神经管道流到肌肉。,当代观点,:,生物电属从导线,半导体等中流动电的基本规律。然而也存在一些区别,生物电与人工电的区别:,6,生物电与人工电的区别,:,生物电与人工电的区别:,7,生物电与人工电的区别,:,生物电与人工电的区别:,8,生物电位测量,生物电位测量,9,细胞膜,磷脂双层膜结构,电容两极板:由亲水的磷脂的头组成。,电容电介质:由疏水的磷脂的尾组成的膜内层。厚度是,3nm,,相对介电常数为,3(,对油而言,),。,可得单位面积电容为:,细胞膜磷脂双层膜结构电容两极板:由亲水的磷脂的头组成。,10,细胞膜,通道(,Channels,)和泵(,Pumps,),Through the,lipid layer,Through proteins passing,thru the lipid layer,细胞膜通道( Channels )和泵( Pumps )T,11,细胞膜,泵(,Pumps,),Na+- K+ Pump,细胞膜泵( Pumps )Na+- K+ Pump,12,Pumps are active processes (i.e., they consume energy) that move ions against the concentration gradients.,The purpose of pumps is to maintain the different intra-and extra-cellular ionic concentrations.,The major ion transporters are: Na+-K+pump, Ca2+pump,.,静息电位,(,或细胞可兴奋性的)影响因素之一,:,Na+-K+pump,(保证细胞膜内外离子浓度差),细胞膜,泵(,Pumps,),细胞膜泵( Pumps ),13,细胞膜内外离子成分,青蛙肌肉,乌贼神经,细胞内,细胞外,细胞内,细胞外,K,+,Na,+,C1,124,4,1.5,2.2,109,77,397,50,40,30,437,556,青蛙肌肉和乌贼神经轴突的,细胞内外离子浓度,(mmol,L),细胞膜内外离子成分青蛙肌肉乌贼神经细胞内细胞外细胞内细胞外K,14,细胞膜内外离子成分,哺乳动物,细胞内外离子成分,细胞膜内外离子成分哺乳动物,15,细胞膜,通道(,Channels,),Bacterial K,+,Channel,细胞膜通道( Channels )Bacterial K+,16,细胞膜,通道(,Channels,),Channels are,passive,processes that allow ions to pass through the membrane under the influence of concentration and electric potential gradients.,Channels exhibit,selective permeability, i.e., they only allow certain ions to pass through them.,Ion channel,gates,regulate the permeability of channels, allowing control over the flow of particular ions.,Key word,:,passive;selectivity; voltage-gated,静息电位,(,或细胞可兴奋性的)影响因素之一,:,通道,(何种离子?什么时候?),细胞膜通道( Channels ),17,浓差电势的形成:,部分,P,+,从,i,室扩散到,e,室,但,Q,-,不能从,i,扩散到,e,室;,扩散引起,e,室内正电荷的积累,(,静电力使这些电荷附于膜上,),,并在,i,室内留下过量的负电荷,(,由于静电力作用,这些电荷聚集于膜的左侧,),,形成了方向为从,e,到,i,的一个电场;,随着,P,+,从,i,扩散到,e,室该电场逐渐增强该增强着的电场不断加深了对扩散的阻抑,直到结束净扩散,达到平衡,浓差电池,:,问题:,什么是平衡?,达到平衡时,浓差电池的电势是多少呢?,浓差电势的形成:浓差电池:问题:,18,Na+-K+pump,(保证细胞膜内外离子浓度差),通道 (何种离子?什么时候?),不同浓度的离子存在,(,Diffusion gradients,),Outwardly or Inwardly-directed electric,field;,温度,这些因素都可以主观地施加影响,静息电位,(,或细胞可兴奋性的),影响因素,静息电位(或细胞可兴奋性的),19,Nernst,电位,The equilibrium potential for any ion X can be calculated from an equation derived in 1888 from basic thermodynamic principles by the German physical chemist Walter Nernst:,where,R,is the gas constant,T,the temperature (in degrees Kelvin),z,the valence of the ion,F,the Faraday constant, and Xo and Xi are the concentrations of the ion outside and inside of the cell.,Nernst电位The equilibrium potent,20,Nernst,电位,Nernst,电位是,一个计算量,,不是测量量。,是针对,单独一种离子,而言的量,所以不能说,“,Nernst,电位是多少,”,,要说成,“,P,离子的,Nernst,电位是多少,”,是某种离子的在给定内外浓度条件下的平衡跨膜电位。,可以这样理解,Nernst,电位:由,Nernst,电位产生一个电场,该电场对离子产生的电场力正好与离子浓度梯度产生的扩散力相平衡。简言之,,Nernst,电位对某种离子作用的电场力与其扩散力相平衡的电位,Nernst电位Nernst电位是一个计算量,不是测量量。,21,Resting Potentials,Equilibrium membrane resting potential when net current through the membrane is zero,P,is the permeability coefficient of the given ion,实际的膜电位是由离子的相对渗透率和离子的浓度决定的,.,任何膜电位的变化是下面两种情况的结果,:,1),膜内,或膜外离子浓度的变化,2),离子渗透率的变化,最后氯离子项分子是胞内浓度,分母是胞外浓度,这是因为氯离子的化合价是,-1.,对单价化合物和双价化合物不能同时使用这个公式,.,Resting PotentialsEquilibrium,22,Action potential recording,刺激器和刺激电极,动作电位记录系统:,记录电极,放大器,处理,显示,实验样本:,蚯蚓,Action potential recording刺激器和,23,Action Potential,Stimulation of excitable cells causes “all-or-none” response,At threshold, the membrane potential rapidly depolarizes due to a change in membrane permeability,P,Na,significantly increases causing the membrane potential to approach E,Na,(+60mV),A delayed increase in P,K,causes hyperpolarization and a return to resting potential,Action PotentialStimulation of,24,动作电位期间,钠的通透性几乎改变了三个数量级,:,P,K,:,P,Na,:,P,Cl,1,0,:,0,04,:,0,45,静息时的膜,P,K,:,P,Na,:,P,Cl,1,0,:,10,0,:,0,45,活动时的膜,理论和实验符合得很好,.,钠的通透性改变在动作电位产生中起重要作用。钠离子通透性上升造成的膜电位有正 的超射。,Hodgkin,的钠离子学说解决了两个问题:,动作电位为什么有超射,即正电位?是离子通透性的改变而不是丧失。尤其是钠离子通透性增大。,动作电位的峰值最大是多少?用,Na,离子的,Nernst,电位估计。,动作电位产生的原因,动作电位期间,钠的通透性几乎改变了三个数量级:动作电位产生的,25,Action Potential and Ionic Conductance,g,Na,and g,K,are the conductance of Na,+,and K,+,v,is the membrane potential,Absolute and relative refractory periods,Action Potential and Ionic Con,26,Circuit Diagram of Membrane,Network,equivalent circuit,of a small increment of membrane,Note critical elements: extracellular-intracelluar,Membrane capacitance, voltage dependent ion channel conductance, reverse potential for each ion channel (Na, K, ),Circuit Diagram of MembraneNet,27,局部电路假说,(,The local circuit hypothesis,),:,解释动作电位是怎样沿神经或细胞传播的。,在没有动作电位传来时,膜内电位比膜外他负。,产生动作电位的区域称为活动区(,Active region,)。其特征是膜电位极性与相反,即内正外负。,膜内、外活动区与非活动区存在电位差,形成局部电流,部分局部电流跨膜,形成电流回路。,无髓神经传导的动作电位,临床上记录的生物电位基本上都是传导的动作电位,局部电路假说无髓神经传导的动作电位 临床上记录的生物电位基本,28,有髓鞘神经纤维的传播,In,myelinated,axons, the AP can,“,jump,”,between myelin sheaths,Open ion channel in,“,node of Ranvier,”,depolarizes neighboring node of Ranvier.,V-gated ion channels in second node will open and generate an AP,有髓鞘神经纤维的传播In myelinated axons,29,Active cell,Volume conductor,A fundamental problem in electrophysiology,Line conductor,生物电容积源和容积导体的概念,Active cellVolume conductorA f,30,人体由复杂器官组成。,容积导体(,Voulme conductor,)是由不同电导率,和介电常数,的,连续的阻性区域,;,心脏和脑,肌肉等组织的可兴奋性的电活动,形成三维容积生物电源(,Volume Source,),I,V,。,生物电容积源和容积导体的概念,人体由复杂器官组成。生物电容积源和容积导体的概念,31,生物电容积源和容积导体的概念,A fundamental problem in electrophysiology is that of the single active cell immersed in a volume conductor .,Volume conductor:,a salt solution simulating the composition of,body fluids.,Complex volume-conductor-field problems:,ENG,EMG, EEG and ECG.,The problem consists of two parts:,the bioelectric source and,its bathing medium or electrical load.,生物电容积源和容积导体的概念A fundamental pr,32,解剖模型,电导率模型,:,解剖模型:几何形状与组织分割,三维重建与表达:成像技术获得数据,电导率模型,:各个区域赋予不同电导率张量,主要模型,:,头,胸部,心脏,有限与无限,均匀与非均匀,各向同性与各向异性,生物电容积源和容积导体的概念,解剖模型电导率模型:生物电容积源和容积导体的概念,33,描述生物容积电源和容积导体中场的量,场强,E,可由标量电位,的负梯度求得,即,:,反过来,已知电场,E,,可求得从从,P1,到,P2,电位的变化为,:,图中,1,2,和,3,那个大,那个小,?,注意电位梯度的方向,描述生物容积电源和容积导体中场的量 场强E可由标量电位的负,34,描述生物容积电源和容积导体中场的量,电流,I,:,为电荷在某一点的流动速率,即单位时间通过,某点,的电荷量:,该量是描述一点电流,没有考虑电流分布于整个体积或一个表面的情况。人体是一个容积导体,所以使用电流不适合于描述生物电流源或电流在人体中的流动规律,。,电流密度,J,:,是矢量,,其方向是电荷流动的方向,大小由垂直于电流方向的截面上每单位面积所通过的电流给定,或者是每单位时间,通过单位面积的电荷给定。单位为,A/m,2,.,根据上述定义,通过,da,的电荷流的速率(电流)为:,描述生物容积电源和容积导体中场的量电流I:为电荷在某一点的流,35,描述生物容积电源和容积导体中场的量,电流源密度,I,V,:,生物体中电流源,是容积电流源,描述这种电源的主要方式是用电流源密度表示,.,表示单位体积产生的电流。单位是,A/m,3,.,电流连续定律,:,在上图中,S,可以是开放的表面、也可以是封闭的表面。假定,S,是包围体积,V,的一个封闭的固定表面,电荷流过表面,S,流出的总速率,必须等于体积,V,内的总电荷减少或增加的总速率,(,即总电流,).,流进,S,内的电流为,:,流出,S,内的电流为,由于区域,V,是任意的,所以有,:,描述生物容积电源和容积导体中场的量电流源密度IV :生物体中,36,欧姆定律,:,电流密度,J,和电场强度,E,之间的关系:,是介质的电导率。,上式只使用于各向同性的均匀线性组织中。事实上,人体组织是各向异性的非均匀的,在有条件的情况下,要考虑这些因素的。,各向异性的结果是电流密度方向和电场方向不一致。,如果电导率是各向异性,这样同样电场强度在不同方向上产生不同的电流密度,描述生物容积电源和容积导体中场的量,欧姆定律 :电流密度J和电场强度E之间的关系:是介质的电导,37,单极子,I,0,置于电导率为,的无限大均匀导电介质中,位于,(x,y,z),。由于导电介质的均匀性,电流线取沿径向的方向,均匀分布。在同心球面上的电流密度是均匀的由于电流的连续性,围绕点电流源为中心的的任意体积内(包括无限小体积内)的,穿过任意半径,r,的球面的总电流必定等于,I,0,:,电流密度,J,就等于,I,0,除以半径为,r,的球,面积,附加说明它的方向即径向方向:,(2.17),可见:,单极子,(monopole),模型及其场,单极子I0置于电导率为的无限大均匀导电介质中,位于 (x,38,单极子,(monopole),模型及其场,代入欧姆定律公式:,积分上式,:,从上式看出,等势面是同心球;在单极子在园心时,电位势的幅度反比于同心球得半径。,单极子(monopole)模型及其场代入欧姆定律公式:积分上,39,偶极子,(Dipole),模型及其场,偶极子,:,由符号相反,强度,I,0,相等,相距很小距离的两个单极子组成。组成偶极子的正单极子称为源,(,source,),负单极子称为阱或汇(,sink,),。,偶极矩,:di,pole moment:,当,d0, I,0, p = I,0,d,保持不变。 偶极矩,p,的方向是与位移,d,的方向一致,都是从阱指向源,.,偶极子(Dipole)模型及其场偶极子:由符号相反,强度I0,40,在场点处偶极场为上述两个单极子场的叠加:,r1,可以用,r,表述为,:,可得偶极场为:,根据方向导数的定义:方向导数等于梯度与方向矢量的点积。所以有:,根据偶极矩的定义:,偶极子,(Dipole),模型及其场,在场点处偶极场为上述两个单极子场的叠加:r1可以用r表述为:,41,由于,所以,如果,p,置于原点,沿,z,轴正方向置放,,则偶极场为:,说明,1),偶极场与单极场比较,偶极场与,(1/,r,)2,成正比,而单极场随变化,所以偶极场衰减的更快。对于给定的,r,,最大的偶极势在极轴上(,z,轴上)。,2),由于有,cos,,偶极场的等势面不是一个同心球面,而更复杂。,偶极子,(Dipole),模型及其场,由于 所以 如果p置于原点,沿z轴正方向置放,说明偶极子(D,42,单根神经(,Single Fiber,)的等价电流源极其场,A long thin fiber is shown embedded in a uniform conducting medium of conductivity ,o,and infinite in extent. The transmembrane current density is described by,i,m,(,x,) so that,i,m,(,x,),dx, illustrated, behaves as a point source in the extracellular medium,单根神经(Single Fiber)的等价电流源极其场 A,43,单根神经(,Single Fiber,)的等价电流源极其场,For a simple monophasic action potential, the associated potential waveform at the outer surface of the membrane is,triphasic in nature,of greater spatial extent than the action potential;,much smaller in peak-to-peak magnitude.,The magnitude of the field potential in a large,bathing medium falls off exponentially with increasing radial distance from the active fiber.,Field potential magnitude at the fiber surface depends on the amount of active cell membrane surface area (bioelectric source) contributing to the signal and is usually on the order of tens of microvolts (,V).,ECG/EEG,单根神经(Single Fiber)的等价电流源极其场For,44,单根神经(,Single Fiber,)的等价电流源极其场,Source:,Active fiber of finite or infinite length with circular cross-section,Conductor:,Infinite, homogeneous,A small element of current,i,m,(,x,),dx,Response: the potential field,单根神经(Single Fiber)的等价电流源极其场Sou,45,单根神经(,Single Fiber,)的等价电流源极其场,The monophasic action potential (the spatial transmembrane voltage of a propagating activation wave),V,m,(,x,) and its second axial derivative ,2,V,m,/,x,2,are shown. As explained in the text, the volume source density is proportional to ,2,V,m,/,x,2,.,单根神经(Single Fiber)的等价电流源极其场The,46,神经干(,Nerve trunk,)的胞外电场,Extracellular field potentials (average of 128 responses) were recorded at the surface of an active (1-mm-diameter) frog sciatic nerve in an extensive volume conductor. The potential was recorded with (a) both motor and sensory components excited (,S,m +,S,s), (b) only motor nerve components excited (,S,m), and (c) only sensory nerve components excited (,S,s).,神经干(Nerve trunk)的胞外电场Extracell,47,心脏的兴奋与传导系统,Sinoatrial (SA) node,Hypopolarized muscle cells, inherent rhythm of contraction, fire 70/80 times per min- this is the pacemaker,Internodal pathways,connect SA node to atrioventricular (A-V) node,A-V node,fires 40/50 times per min,slow conduction velocity,delays SA signal before passing it on to the ventricles,very few gap junctions in these muscle cells,His bundle,carries signal to Purkinje fibers,Purkinje fibers,conveys signals across ventricle, fire 15/40 times per minute,心脏的兴奋与传导系统 Sinoatrial (SA) nod,48,心脏的兴奋与传导系统,心脏的兴奋与传导系统,49,The different waveforms of the specialized cells,in the heart,心肌细胞动作电位,The different waveforms of the,50,The difference of action potentials,between skeletal muscle or neuron and cardiac muscle,lies in the special role of,voltage-gated Ca+,slow channels in cardiac muscle.,心肌细胞动作电位,The difference of action poten,51,心肌细胞间的连接,外形,:,呈圆柱型,其长,100 m,,直径,15m,排列:,成砖状结构,连接:,端端型,相向的细胞膜形成,润盘(,intercalated discs,)的结构,心肌细胞间的连接外形:,52,Gap junction,:,Gap junction channel consist of two connexons aligned end-to-end, forming a cytoplasm-filled connection between the interior of two cells.,Each connexon consists of six hexagonally arranged protein subunits, or connexins.,The pore is a hydrophilic channel between two cytoplasms,Plasma membranes come within 2-4nm of each other,心肌细胞间的连接,Gap junction:心肌细胞间的连接,53,心脏的行为象某种功能合胞体,(,functional syncytium,),Functional syncytium,:,通过间隙连接(,gap junctions,)兴奋在心肌中从细胞到细胞接触着传播 通过桥粒和紧连接,机械上成为一个整体,two syncytia,- atrial and ventricle; connected by AV bundle, specialized fibers conducting impulses between atria and ventricles,心肌细胞间的连接,心脏的行为象某种功能合胞体(functional syncy,54,心向量,体表电位,导联向量,偶极子:同样强度,相距很近的一个点电流源和一个点电流汇组成,双电层,:,在体积导体内部,任意形状的光滑面(意味着厚度为零)上,分布有偶极子源形成的面偶极子源就双电层源(,Double layer source),心肌纤维的激活波是一个等效的双层源,Structure of a double layer. The double layer is formed when the dipole density increases to the point that it may be considered a continuum. In addition, we require that,J,d,0, and,Jd,p,.,心向量,体表电位,导联向量偶极子:同样强度,相距很近的一个点,55,心向量,Cardiac Vector,(,Heart Vector,),(Dipole),在心脏激活时的任何时刻源都是许多双层电源。每一双层电源等效为取曲面法向,(,且向外,),的偶极子。这样激活心脏的源是空间分布的偶极子,.,空间分布的偶极子可以是离散的,偶极矩分别是,p,1,,,p,2,,,.,p,n,.,可以等于一个总的偶极矩,H,即,:,=,平 移,=,相 加,和矢量,心向量Cardiac Vector(Heart Vecto,56,心向量,(,或心偶极子,),把所有离散分布的和连续,分布的,等效偶极子成分总和起来的为一个单个的偶极子就称为心偶极子或心向量,.,心向量位于什么地方,?,“,中心偶极子,”,假定,:,在躯干的电位可以假定产生于一个集中偶极子即心向量,H,,位于驱干的中心,这个集中偶极子矩等于各个纤维偶极子源的矢量和或矢量积分,.,心向量,Cardiac Vector,(,Heart Vector,),(Dipole),心向量(或心偶极子)“中心偶极子”假定:心向量Cardia,57,体表电位,The heart is viewed as an electrical equivalent generator,.(,激励),thoracic volume conductor,(线性系统),Potentials measured at the outer surface of this medium,that is, on the body surface-are referred to as electrocardiograms, or ECGs.,(响应),体表电位The heart is viewed as an,58,体表电位,The electrocardiography problem,Points A and B are arbitrary observation points on the torso,R,AB,is the resistance between them, and,R,T1,R,T2,are lumped thoracic medium resistances. The bipolar ECG scalar lead voltage is,A,-,B, where these voltages are both measured with respect to an indifferent reference potential.,体表电位The electrocardiography pr,59,导联向量,导联:,A pair of electrodes, or combination of several electrodes through a resistive network that gives an equivalent pair, is referred to as a lead,导联电压,:两体表电极之间测量的电压。,偶极子场情况:,影响导联电压的三个因素:,源:心向量,H,几何:导联位置与心向量之间的相对位置,组织电特性:电导率分布,导联向量导联:A pair of electrodes, o,60,偶极子场情况,,将源与其它因素分离,导联向量,更一般情况:,它表明导联电压,(响应)取决于心脏向量(源)和第二个向量,L,(传递函数,具有阻抗量纲,称为跨阻传递函数,)。这个,L,向量称为导联向量。,对于给定的导联位置如果心向量位置有变化,那么在每一个这种位置的,l,也将不同。在这种情况下,,L,是一个向量场,。,偶极子场情况,将源与其它因素分离导联向量更一般情况:它表明导,61,标准导联,(Eindhvon,Triangle),标准或肢体导联是由,Einthoven(,心电图之父,),最先提出来的,它是把电极放置在肢体末端,右足通常接地以帮助降低噪声,余下的末端电位配对给出下面三种,(,导联,),电压:,V,I,= ,LA, ,RA,V,II,= ,LL,RA,V,III,= ,LL,- ,LA,式中,RA,是右臂,,LA,是左臂,,LL,是左足,由,LA,- ,RA,代表左臂相对于右臂的电位,(,命名为导联,V,I,),。,标准导联(Eindhvon Triangle)标准或肢体导,62,导联电压之间的关系:,各导联电压,(V,,,V,,,V,),计算:,由心向量在各个的导联向量上的投影,(,并和导联向量的大小相乘)求出,。,导联向量:形成一个等边三角形,(Einthoven,假定),标准导联,(Eindhvon,Triangle),导联电压之间的关系:各导联电压(V,V,V)计算:导联,63,标准导联,(Eindhvon,Triangle),标准导联(Eindhvon Triangle),64,WILSON CENTRAL TERMINAL:,三个,5k,每一个电阻的另一端连接到不同的肢体导联,电阻的公共连接点做为导联参考点。每一个肢体导联流入,CT,的电流之和就必定趋于零。如果,CT,表示中心电端电位,有,:,解出,CT,得到下式,:,单极导联,参考电极,Wilson central terminal,WILSON CENTRAL TERMINAL:解出CT得,65,增强导联与胸导联,,12,导联,增强导联与胸导联,12导联,66,The sites of electrode placement on the precordium,The “Precordial Leads”,增强导联与胸导联,,12,导联,The sites of electrode placeme,67,The most commonly used clinical ECG-system, the 12-lead ECG system, consists of the following 12 leads, which are:,I, II, III,aV,R, aV,L, aV,F,V,1, V,2, V,3, V,4, V,5, V,6,增强导联与胸导联,,12,导联,The most commonly used clinica,68,
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