心电活动的可视并行计算模型
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
准确阐明正常与各种异常心电图如何产生于心肌细胞的电活动和考察各种心律失
    常的形成与持续机制对于心脏疾病的诊断具有重要意义。由于受临床与实验手段的限
    制,对于心电学领域中存在的许多不清楚和有争议的问题,建模与仿真一直是一个受
    到高度重视的研究手段。迄今为止,大多数的心电模型以经典的Miller-Geselowitz模
    型为基础,使用偶极子表达抽象的心肌细胞的电活动,并由偶极矩计算场点电势得到
    仿真心电图。其它重要的模型种类包括电生理模型和使用Fitzhugh-Nagumo方程考察
    心律失常动力学性质的模型。已报道的电生理模型都是一维和二维的多细胞模型,旨
    在详细考察细胞间连接通讯与兴奋传播的关系,未与体表心电图联系起来。大规模并
    行计算是发展全心脏电生理模型的主要障碍,所涉及的问题有两个方面,即如何高效
    地执行和如何方便地描述几千至几百万组心肌细胞动作电位方程的并行求解。
     细胞自动机是一种完全并行的计算模式,具有固有的并行性,作为离散动力学仿
    真系统近年来受到广泛注意。尽管按标准定义的细胞自动机是基于规则的,但可以有
    基于语言的实现,使之具备更灵活的描述能力。作为建模的前提,我们对一种基于语
    言实现的细胞自动机系统Cellular3.0在语言和可视化设施方面进行了扩展,使之能
    够描述大规模并行数值计算。
     为了在细胞与亚细胞层次精细地和可视化地考察心电图的产生与心律失常的形
    成,我们使用经扩展的Cellular3.0为工具设计与实现了一个全心脏电生理模型,该模
    型的两个构成要素分别是细胞自动机式的大规模并行计算和各种心肌细胞的动作电位
    模型。所包含的心肌组织为窦房结、房室结、心房肌、心室肌、心房传导束以及心室
    传导束。限于我们现有计算机的性能,模型是二维的,包含五千余个细胞。根据心室
    的分层特性以及不同层次细胞具有不同电学性质的事实,我们提出了一个与模型解析
    度和几何特性无关的运行时心壁分层算法,将室壁分层以及使心肌细胞的电活动与其
    所在层次联系起来。兴奋在同层细胞间是沿轴向端到端传导,在不同层细胞间是沿径
    向边到边传导,两种传导具有不同的速度。细胞间共有24种跨缝隙连结结构,用于
    准确描述各种细胞间不同的兴奋传导特性。靠并行求解数千组心肌细胞动作电位方程
    和计算各个细胞对之间的跨结兴奋传播,心电活动的时空过程,包括许多心律失常的
    形成与演绎过程,能够得到可视化地展现。单个心肌细胞的电活动可使用跟踪窗口进
    行跟踪与显示。对于建模中所遇到的问题我们也进行了讨论。
     基于全心脏电生理模型,我们还提出了一个新的心电图仿真算法,在细胞层次计
    算每一个处于相互连接与通讯中的心肌细胞对各种导联位置心电图的贡献,仿真的正
    常与多种异常心电图波形与临床记录十分一致。根据仿真结果,我们讨论了若干心电
    图波形的形成机制及诊断意义,包括右胸R波的意义、病理性Q波的形成机制和一
    
    
     侧
     心室电活动对对侧胸表心电场的影响,处于不同位置心肌细胞动作电位波形变井’3
     心电图波形变异之间的关系得到形式和定量的说明。已完成的仿真表明该模型对十考
     察心律失常的形成具有极大的助益,论文给出了若干心律失常的仿真例,包括缺血诱
     导的心动过速及M纠1胞独特的电学性质在心律失常形成中。】能起到的作川。
     最后,我们简要讨论了大规模多层次并行i;算在解决广泛存在的复杂性问题方面
     的作川,心电问题只是生物医学领域中复杂性问题的一个典型例了。
Answering how normal and various abnormal ECGs generate from the electrical
     activities of cardiac cells and investigating how various arrhythmias form and sustain have
     been questions of great significance to the diagnosis of heart diseases. Restricted by the
     limited means of clinical and experimental investigation, quite a few of unclear and
     debatable questions in cardioelectricity still exist and modeling and simulation has been
     valued as an important research approach. So far, most cardioelectrical models have been
     built based on the classical Miller-Geselowitz model that employs a dipole to represent the
     electrical activity of each abstract cardiac cell. Other kinds of models include the
     electrophysiological models and the models employing the Fitzhugh-Nagumo equation to
     investigate the dynamic behavior of arrhythmia. The reported electrophysiological models
     are one- or two-dimensional multicellular models, aiming at investigating the intercellular
     connection and communication, but lacking an imbedded ECG computing algorithm to link
     the cardioelectrical activity with the recordings of ECG. The massive parallel computing has
     been the main obstacle to develop a whole-heart electrophysiological model. Difficulties
     come from two aspects: the efficiency of executing and the convenience of describing
     thousands to millions groups of nonlinear action potential equations of cardiac cells.
    
     As a computation mode with intrinsic parallel features, cellular automata have received
     increasing attentions in recent years as the tool of discrete dynamic system simulation.
     Although the standard defined cellular automata are rule-based, they can be implemented as
     languages, with much flexibility in computation describing. As the basis of our work, we
     made extensions to both the language compiler and the viewing facility of Celltilae3.O, a
     language-based cellular automata system, and made it applicable to describe the massive
     parallel numerical computing.
    
     To investigate the ECG generation and the arrhythmia formation problems
     quantitatively and visibly at cellular and subcellular level, taking the extended cellular3.O as
     tool, we designed and implemented a whole-heart electrophysiological model. The two key
     components of this model are the cellular automata style massive parallel computing and the
     action potential models of cardiac cells. The included cardiac tissues are sinoatiial node,
     atrioventricular node, atrium, ventricle, intra-atrial conduction bundle, and intra-ventricular
     conduction bundle (Purkinje fiber). Restricted by the power of computer we equip now, the
     current model is two-dimensional now and consists of about more than four thousand
     cardiac cells. According to the fact that the walls of ventricles are layered and cells at
    
    
    ND
     different layer have different electrical properties, we developed a resolution- nd geometry-
     independent run-time make-layer algorithm to layer the was of ventricles, linking the
     electrical property of cardiac ll with its layer position. The excitation propagation among
     cells of same layer is end-to-end conduction along longitudinal direction and the
     propagation among cells of different layer is side-to-side conduction along radial direction.
     Twenty-four kinds of intercellular gap junctions are designed to describe the intercellular
     excitation propagation among cells of different kinds and cells along different direction. By
     parallely solving thousands groups of action potential equations of cardiac cells and
     computing the trans-junctional excitation propagation between every cell pairs, the
     spatiotemporal process of ca
引文
[l]Burger HC, van Milaan JB. Heart-vector and leads:Part Ⅰ. British Heart Journal. 1946:8:157-161.
    [2] Burger HC, van Milaan JB. Heart-vector and leads:Part Ⅱ. British Heart Journal. 1947;9:154-160.
    [3] Frank E. Absolute quantitative comparison of instantaneous QRS equipotentials on a normal subject with dipole potentials on a homogeneous torso model. Circulation Research. 1955;3:243-251.
    [4] McFee R, Parungao A. An orthogonal lead system for clinical electrocardiography. American Heart Journal. 1961 ;62:93-100.
    [5] Brody DA, Romans WE. A model which demonstrates the quantitative relationship between the electromotive forces of the heart and the extremity leads. American Heart Journal. 1953;45:263-276.
    [6] Bayley RH, Berry PM. Changes produced in the resultant "heart" vector by the non-homogeneous volume conductor with normal specific resistivities. In: Hoffman , Taymor RC. eds. Vectorcardiography. North-Holland. 1966;p109-118.
    [7] Bayley RH, Kalbfleisch JM, Berry PM. Changes in the body' s QRS surface potentials produced by alterations in certain compartments of the nonhomogeneous conducting model. American Heart Journal. 1969;77:517-528.
    [8] Rudy Y, Plonsey R. The eccentric spheres model as the basis for a study of the role of geometry and inhomogeneities in electrocardiography. IEEE Trans. Biomedical Engineering. 1979;26:392-399.
    [9] Gulrajani RM, Roberge FA, Mailloux GE. The forward problem of electrocardiography. In: MacFarlane PW, Lawrie TDV. eds. Comprehensive electrocardiology. Pergamon Press. 1989.
    [10] Miller WT Ⅲ, Geselowitz DB. Simulation studies of the electrocardiogram. Ⅰ. The normal heart. Circulation Research. 1978;43:301-315.
    [11] Geselowitz DB, Miller WT Ⅲ. Active electric properties of cardiac muscle. Bioelectromagnetics. 1982;3:127-132.
    [12] Geselowitz DB, Miller WT Ⅲ. A bidomain model for anisotropic cardiac muscle. Annals of Biomedical Enginnering. 1983;11:191-206.
    [13] Geselowitz DB. Theory and simulation of the electrocardiogram. In: MacFarlane PW. Lawrie TDV. eds. Comprehensive electrocardiology. Pergamon Press. 1989.
    
    
    [14]Durrer D et al. Total excitation of the isolated human heart. Circulation. 1970;41:899-912.
    [15]Lorange M, Gulrajani RM. A computer heart model incorporating myocardial anisotropy. I.Model construction and simulation of normal activation. Journal of Electrocrdiology.1993;26:245-261.
    [16]Lorange M, Gulrajani RM, Nadeau RA. A computer heart model incorporating anisotropic propagation. Ⅱ. Simulations of conduction block. Journal of Electrocardiology.1993;26:263-277.
    [17]Xu Z, Gulrajani RM, Molin F. A computer heart model incorporating myocardial anisotropy.Ⅲ. Simulation of ectopic beats. Journal of Electrocardiology. 1996;29:73-90.
    [18]Dube B, Gulrajani RM, Lorange M. A computer heart model incorporating anisotropic propagation, Ⅳ. Simulation of regional myocardial ischemia. Journal of Electrocardiology.1996;29:91-103.
    [19]Gulrajani RM. The forward and inverse problems of electrocardiography. IEEE Engineering in Medicine and Biology. 1998;Sept/Oct. 84-101.
    [20]Lu WX, Xia L. Computer simulation of epicardial potentials using a heart-torso model with realistic geometry. IEEE Trans. Biomedical Engineering. 1996;43:211-217.
    [21]李光林,夏灵,吕维雪.心电逆问题的虚拟心脏模型参数解用于心室预激旁道定位的研究生物物理学报 1997;13:420-426.
    [22]Siregar P, Sinteff JP, Chahine M, Le Beux P. A cellular automata model of the heart and its coupling with a qualitative model. Computer and Biomedical Research. 1996;29:222-246.
    [23]Siregar P, Chahine M, Lemoulec F. An interactive qualitative model in cardiology. Computer and Biomedical Research. 1995;28:443-478.
    [24]Spach MS, Heidlage JF. A multidimensional model of the cellular effects on the spread of electrotonic currents and on propagating action potentials. Cirtical Review on Engineering.1992;20:141-169.
    [25]Thakor NV, Ferrero JM Jr, Saiz J, et al. Electrophysiologic models of heart cells and cell networks. IEEE Engineering in Medicine and Biology. 1998; Sept/Oct. 73-83.
    [26]Cabo C, Pertsov AM, et al. Wave-front curvature as a cause of slow conduction and block in isolated cardiac musle. Circulation Research. 1994;75: 1014-1028.
    [27]Seydel R. Practical bifurcation and stability analysis. Springer-Verlag. 1994.
    [28]Gray RA, Pertsov AM, Jalife J. Incomplete reentry and epicardial breakthrough patterns during atrial fibrillation in the sheep heart. Circulation. 1996;94:2649-2661.
    [29]Keener JP, Panfilov AV. A biophysical model for defibrillation of cardiac tissue. Biophysical Journal. 1996;71:1335-1345.
    
    
    [30]Pollard AE, Burgess MJ, Spitzer KW. Computer simulation of three-dimensional propagation in ventricular myocardium. Circulation Research. 1993;72:744-756.
    [31]Abboud S, Berenfeld O, Sadeh D. Simulation of high-resolution QRS complex using a ventricular model with a fractal conduction system. Circulation Research. 1991;68:1751-1760.
    [32]Winfree AT. Electrical turbulence in three-dimensional heart muscle. Science.1994;266:1003-1006.
    [33]Gray RA, Jalife J, Panfilov AV,et al. Mechanisms of fibrillation. Science. 1995;270:1222-1225.
    [34]Holden AV. The restless heart of a spiral. Nature. 1997;387:655-655.
    [35]Gray RA,Pertsov AM,Jalife J. Spatial and temporal organization during cardiac fibrillation.Nature. 1998;392:75-78.
    [36]Witkowski FX et al. Spatiotemporal evolution of ventricular fibrillation. Nature.1998;392:78-82.
    [37]Cohen ME, Hudson DL, Deedwania PC. Applying continuous chaotic modeling to cardiac signal analysis. IEEE Engineering in Medicine and Biology. 1996; Sept/Oct. 97-102.
    [38]Otakar F, Holcik J. Applying nonlinear dynamics to ECG signal processing. IEEE Engineering in Medicine and Biology. 1998; Mar/Apr. 96-101.
    [39]Kasmacher-Leidinger H, Schmid-Schonbein H. Complex dynamic order in ventricular fibrillation. Journal of electrocardiology. 1994;27:287-299.
    [40]张辉,等.非线性动力学在心脏活动研究中的应用,生物物理学报.1997;13:340-346.
    [41]Spach MS. Microscopic basis of anisotropic propagation in the heart. In: In: Zips DL, Jalife J. eds. Cardiac electrophysiology: From cell to bedside. Second edition. W.B. Saunders Company. 1995.
    [42]Hobble RK. Intermediate Physics for Medicine and Biology. John Wiley & Sons. 1978.
    [43]Hodgkin, A.L. & Huxley, A.F. A quantitative description of membrane current and its application to conduction and excitation in nerve. Journal of Physiology. 1952;117:500-544.
    [44]Rush S, Larsen H. A practical algorithm for solving dynamic membrane equations. IEEE Trans. on Biomedical Engineering. 1978;25:389-392.
    [45]Beeler GW, Reuter H. Reconstruction of the action potential of ventricular myocardial fibres.Journal of Physiology. 1977;268:177-210.
    [46]Mcallister RE, Noble D, Tsien RW. Reconstruction of the electrical activity of cardiac purkinje fibres. The Journal of Physiology. 1975; 251:1-59.
    [47]DiFrancesco D, Noble D. A model of cardiac electrical activity incorporating ioric pumps
    
    and concentration changes. Philos. Trans. R Sbc Lond Biology. 1985;307:353-398.
    [48] Luo C, Rudy Y. A model of the ventricular cardiac action potential. Circulation Research. 1991;68:1501-1526.
    [49] Luo CH, Rudy Y. A dynamic model of the cardiac ventricular action poiential Ⅱ. Afterdepolarizations, trigger activity, and potentiation. Circulation Research. 1994;74:1097-1113.
    [50] Luo CH, Rudy Y. A dynamic model of the cardiac ventricular action potential Ⅰ. Simulation of ionic currents and concentration changes. Circulation Research. 1994;74:1071-1096.
    [51] Demir SS, Clark JW, Giles WR. Parasympathetic modulation of sinoatrial node pacemaker activity in rabbit heart: a unifying model. American Journal of Physiology. 1999; 45:H2221-H2244.
    [52] Liu, Y. et al, lonic mechanisms of electrotonic inhibition and concealed conduction in rabbit atrioventricular nodal myocytes. Circulation. 1993; 88:1635-1646.
    [53] von Neumann J. Theory of self-reproducing automata. Edited and completed by Burks AW. University of Illinois Press. 1966.
    [54] Ermentrout GB, Edelstein KL. Cellular automata approaches to biological modeling. Journal of Theoratical Biology. 1993; 160:97-133.
    [55] Wolfram S. Cellular automata as models of complexity. Nature. 1984; 311:419-424.
    [56] Wolfram, S. Theory and application of cellular automata. World Scientific Singapo e. 1986.
    [57] Gutowitz H. Cellular automata: theory and experiment. Physica D.1990;45.
    [58] Toffoli, T. & Margolis, N. Cellular automata machine: A new environment for modeling. MIT Press. 1987.
    [59] Chopard B. Droz M. Cellular automata modeling of physical systems. Cambridge University Press. 1998.
    [60] Omohundro S. Modeling cellular automata with partial differential equations. Physica 10D. 1984; 128-134.
    [61] Simons NRS, Cuhaci M. On the potential use of cellular automata machines for electromagnetic field solution. International Journal of Numerical Modeling : Electronic Networks, Devices and Fields. 1995;8:301-312.
    [62] Silveira PSP, Massad E. Modeling and simulating morphological evolution in ar artificial life environment. Computers and Biomedical Research. 1998;31:1-17.
    [63] Zhu H, Yin B, Cao L. (朱浩,尹炳生,曹琳) Parallely solving millions of differential equations with cellular automata. The Proceedings of the Fourth International Conference on System Simulation and Scientific Computing. Beijing, 1999.
    
    
    [64] Yanagihara, K. Noma, A. & Irisawa, H. Reconstruction of sino-atrial node pacemaker potential based on the voltage clamp experiments. Japanese Journal of Physiology. 1989;30:841-857.
    [65] Liu Y, Zeng W, Delmar M, Jalife J. Ionic mechanisms of electrotonic inhibition and concealed conduction in rabbit atrioventricular nodal myocytes. Circulation. 1993; 88:1635-1646.
    [66] Nygren A, Fiset C, Firek L, Clark JW, Lindblad DS, Clark RB, Giles WR. Mathematical model of an adult human atrial cell. Circulation Research. 1998; 82:63-81.
    [67] Veenstra RD. Physiology of cardiac gap junction chnnels. In: Zipes DP. Jalife J, eds. Cardiac electrophysiology: From cell to bedside. First edition. W.B. Saunders Company. 1990.
    [68] Pressler ML, Munster PN, Huang X. Gap junction distribution in the heart: Functional relevance. In: Zipes DP, Jalife J. eds. Cardiac electrophysiology: From cell to bedside. Second edition. W.B. Saunders Company. 1995.
    [69] Antzelevitch C, Sicouri S. Clinical relevance of cardiac arrhythmias generated by afterdepolarizations. Journal of American Collage Cardiology. 1994;23:259-277.
    [70] Whalley DW, Wendt DJ, Grant AO. Electrophysiologic effects of acute ischemia and reperfusion and their role in the genesis of cardiac arrhythmia. In: Podrid PJ, Kowey PR. eds. Arrhythmia: Mechanisms, diagnosis, and management. Wiliams & Wilkins. 1995.
    [71] Samuels F, Hessen SE, Dreifus LS. Reentry and development of arrhythmia: Preclinical and clinical data. In: Podrid PJ, Kowey PR. eds. Arrhythmia: Mechanisms, diagrosis, and management. Wiliams & Wilkins. 1995.
    [72] Jongsma HJ, Rook MB. Morphology and electrophysiology of cardiac gap junction channels. In: Zips DL, Jalife J. eds. Cardiac electrophysiology: From cell to bedside. Second edition. W.B. Saunders Company. 1995.
    [73] Myerburg RJ, Demirovic J. Sudden cardiac death/ventricular fibrillation. In: Podrid PJ, Kowey PR. eds. Cardiac arrhythmia: Mechanisms, disgnosis, and management. Williams & Wilkins. 1995.
    [74] Surawicz B. U wave: facts, hypotheses, misconceptions, and misnomers. Journal of Cardiovascular Electrophysiology. 1998;9:1117-1128.
    [75] Shahidi AV, Savard P, Nadeau R. Forward and inverse problems of electrocardiography: modeling and recovery of epicardial potentials in humans. IEEE.Trans, on Biomedical Engineering. 1994; 41:249-256.
    [76] Macleod RS, Brooks DH. Recent progress in inverse problems in electrocardiology. IEEE Engineering in Medicine and Biology. 1998;Jan/Feb. 73-83.
    
    
    [77] Antzelevitch C, Sicouri S, Lukas A, DiDiego JM, Nesterenko VV, Liu DW, Roubache JF, Zygmunt AC, Zhang ZQ, lodice A. Clinical implications of electrical heterogeneity in the heart: The electrophysiology and pharmacology of epicardial, M, and endocardial cells. In: Podrid PJ, Kowey PR. eds. Arrhythmia: Mechanisms, diagnosis, and management. Wiliams & Wilkins. 1995.
    [78] Geselowitz DB. Dipole theory in electrocardiography. American Journal of Cardiology. 1964; 14,:301-306.
    [79] Gerlernter HL, Swihart JC. A mathematical-physical model of the genesis of the electrocardiogram. Biophysical Journal. 1964; 4:285-301.
    [80] Holland RP, Arnsdorf MF. Solid angle theory and the electrocardiogram: physiologic and quantitative interpretations. Progress in Cardiovascular Diseases. 1977; 19:431-45 7.
    [81] Taggart P, Sutton P, Pugsley W, Swanton H. Repolarization gradients derived by subtraction of monophasic action potential recordings in the human heart. Journal of Electrocardiology. 1995; 28 Supplement: 156-161.
    [82] Noble D, Cohen I. The interpretation of the T wave of the electrocardiogram. Cardiovascular Research. 1978; 12:13-27.
    [83] Inoue M, Hori M, Kajiya F, Kusuoka H, Abe H, Furukawa T, Takasugi S. Theoretical analysis of T-wave polarity based on a model of cardiac electrical activity. Journal of Electrocardiology. 1978; 11:171-180.
    [84] Franz MR, Bargheer K, Rafflenbeul W, Haverich A, Lichtlen PR. Monophasic action potential mapping in human subjects with normal electrocardiograms: direct evidence for the genesis of the T wave. Circulation. 1987; 75:379-386.
    [85] Witkowski FX, Kavanagh KM, Penkoske PA, Plonsey R. Epicardial cardiac source-field behavior. IEEE Trans, on Biomedical Engineering. 1995; 42:552-558.
    [86] Barnard ACL, Duck IM, Lynn MS. The application of electromagnetic theory to electrocardiology I. Derivation of the integral equations. Biophysical Journal. 1967;7:443-462.
    [87] MacFarlane PW, Lawrie TDV. Comprehensive electrocardiology. Pergamon Press. 1989.
    [88] Plonsey R. Volume conductor fields of action currents. Biophysical Journal. 1964;4:317-328.
    [89] Tinniswood AD, Furse CM, Gandhi OP. Power deposition in the head and neck of an anatomically based human body model for plane wave exposures. Physics in Medicine and Biology. 1998;43:2361-2378.
    [90] Oosterom AV. Cell models-macroscopic source descriptions. In: MacFarlane PW, Lawrie
    
    TDV. eds. Comprehensive electrocardiology. Pergamon Press. 1989.
    [91]杨均国,李治安.主编 现代心电图学.科学出版社.1997;p,197.
    [92]Hoffman BF, Cranefield P. Electrophysiology of the heart. McGraw-Hill. 1960; p202.
    [93]Nahum LH, Hoff HE. The interpretation of the U wave of the electrocardiogram. American Heart Journal. 1939; 17:585-598.
    [94]Lazzara R. The U wave and the M cell. Journal of American College Cardiology.1995;26:193-194.
    [95]马向荣编.临床心电图学词典(第二版).解放军医学出版社.1995.
    [96]Glass LS, Mackey MC. From clocks to chaos: The rhythms of life. Princeton University Press. 1988.
    [97]Kaplinsky E, Ogawa S, Balke CW, Dreifus LS. Two periods of early ventricular arrhythmia in the canine acute myocardial infarction model. Circulation. 1979;60:397-403.
    [98]Dominguez G, Fozzard HA. Influence of extracellular K~+ concentration on cable properties and excitability of sheep cardiac Purkinje fibres. Circulation Research. 1970;26:565-574.
    [99]Buchanan JW Jr, Saito T, Gettes LS. The effects of antiarrhythmic drugs, stimulation frequency, and potassium-induced resting, membrane potential changes on conduction velocity and dV/dt_(max), in guinea pig myocardium. Circulation Research. 1985;56:696-703.
    [100]Janse M J, van Capelle FJL, Morsink H, et al. Flow of injury current and patterns of excitation during early ventricular arrhythmias in acute regional myocardial ischemia in isolated porcine and canine hearts. Evidence for two different arrhythmogenic mechanisms. Circulation Research. 1980;47:161-165.
    [101]Antzelevitch C, Sicouri S, Litovsky SH, et al. Heterogeneity within the ventricular wall:electrophysiology and pharmacology of epicardial,endocardial and M cells. Circulation Research. 1991 ;69:1427-1449.
    [102]Liu DW, Antzelevitch C. Characteristics Of the delayed rectifier current in canine ventricular epicardial, midmyocardial, and endocardiai myocytes. Criculation Research.1995;76:151-165.
    [103]Gallagher R, Appenzeller T. Beyond reductionism. Science. 1999;284:79-79.
    [104]Chialvo DR, Jalife J. On the non-linear.equilibrium of the heart: Locking behavior and chaos in Purkinje fibres, in: Zipes DP, Jalife J. eds. Cardiac electrophysiology: From cell to bedside. First edition. W.B. Saunders Company. 1990.
    [105]Goldenfeld N, Kadanoff LP. Simple lessons from complexity. Science. 1999;284:87-89.
    [106]Weng G, Bhalla US, lyengar R. Complexity in biological signaling systems. Science.1999;284:96-98.
    
    
    [107]Bhalla US, lyengar R. Emergent properties of networks of biological signaling pathways.Science. 1999; 283:387-392.
    [108]Rind D. Complexity and climate. Science. 1999;284: 105-107.
    [109]PIonsey R, Henriquez CS. Limitations in the use of one-dimensional electrophysiological models for multicellular tissue. In: Zipes DP, Jalife J. eds. Cardiac electrophysiology: From cell to bedside. First edition. W.B. Saunders Company. 1990.
    [110]Guevara MR, Shrier A, Glass L. Chaotic and complex cardiac rhythms. In: Zipes DP, Jalife J. eds. Cardiac electrophysiology: From cell to bedside. First edition. W.B. Sat, nders Company. 1990.
    [111]Ramon PCC, Huntsman LL, Bardy GH, Kim Y. On the contribution of volume currents to the total magnetic field resulting from the heart excitation proess: A simulation study. IEEE Trans. on Biomedical Engineering. 1996;43:95-103.
    [12]杨均国,李治安.主编 现代心电图学.科学出版社.1997;p153.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700