跳到主要內容

簡易檢索 / 詳目顯示

研究生: 李度門
Le Duy Manh
論文名稱: Predicting Self-terminating Ventricular Fibrillation by Bivariate Data Analysis and Controlling Cardiac Alternans by Chaotic Attractors
Predicting Self-terminating Ventricular Fibrillation by Bivariate Data Analysis and Controlling Cardiac Alternans by Chaotic Attractors
指導教授: 黎璧賢
陳志強
口試委員:
學位類別: 博士
Doctor
系所名稱: 理學院 - 物理學系
Department of Physics
論文出版年: 2014
畢業學年度: 102
語文別: 英文
論文頁數: 101
中文關鍵詞: 複雜動力學心臟心律不整之失穩回饋控制混沌吸引子
外文關鍵詞: Complex dynamics, Heart, Arrhythmias, Instability, Feedback control, Chaotic attractor
相關次數: 點閱:19下載:0
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報
  • 心臟乃包含多成員共同協調工作以達成心律及血氧、養份傳輸至全身之複雜動力學系統。在急速電刺激下,心臟會出現因失穩而產生如交替心律、心動過速及心律不整之豐富動力行為。本論文將呈現我們在體外大鼠全心臟分析心室顫抖數據及抑制交替心律上的成果。我們對體外全心臟在Langendorff系統以急速電刺激引發心室顫抖並同時測量右心房及左心室之電訊號。我們以新穎之非線性分析時間序列方法發現心室顫抖自行復元之先兆,有高達八至九成的成功預測率,並了解其機制。我們以微干擾回饋控制來抑制交替心律之幅度,提出非線性疊代函數理論模型及離子通道模型以理解其機制並以體外大鼠全心臟實驗驗證其詳細之動力學。其控制機制仍源於其微細混沌吸引子之行為,有別於傳統之回饋控制方法與概念。


    Heart is a complex dynamical system that contains many components worked
    rhythmically in a coordinated manner to produce rhythmic activity for effectively
    pumping blood, feeding activities of the whole living body with nutrition and
    oxygen. Under fast electrical pacing, heart shows rich dynamical behaviors due
    to its instability, such as alternans, tachycardia and fibrillation. In this thesis, we
    will present our works in data analysis of ventricular fibrillation and suppressing of
    cardiac alternans by alternating-period-feedback stimulations of a whole isolated
    rat heart.
    Ventricular fibrillation (VF)is an extremely serious arrhythmia which is known to
    be the major cause of sudden cardiac death, and thus the research to understand
    its mechanism as well as clinical treatments is very important. In our study, VF
    in isolated hearts perfused in the Langendorff system is induced by fast electrical
    pacing. Electrical signals from right atrium (a site very closed to sinoatrial node)
    and left ventricle are recorded simultaneously. We find that when there is strong
    component of ventricular signal detected in the atria one during VF, the induced
    VF is usually not self-terminating. Quantitative criteria for the prediction ofself-
    terminating VF are proposed based on the analysis of bivariate time series (atrial
    and ventricular signals)bythe cross-wavelet and cross-Fourier power spectra meth-
    ods. The success rate of our prediction is about 80-90%. Our findings suggest that
    a heart under VF can recover its sinus rhythm only when the sinoatrial node of
    the heart is not under strong influence of the VF from its ventricle.
    Alternans response, comprising a sequence of alternating long and short action
    potential durations or strong and weak contractions in the heart tissue, seen dur-
    ing rapid periodic pacing can lead to conduction block resulting in potentially
    fatal cardiac failure. A method of pacing with feedback control is proposed to
    reduce the alternans and therefore the probability of subsequent cardiac failure.
    The reduction is achieved by feedback control using small perturbations of con-
    stant magnitude to the original alternans-generating pacing period T, viz., using
    sequences of two periods of T+ǫ and T−ǫ, with ǫ ≪ T. This scheme for alternans
    suppression is demonstrated experimentally in isolated whole heart experiments
    and further confirmed and investigated in detail by simulations of an iterated map
    and also ion-channel based models of cardiac myocytes. The mechanism of the
    success of our method is explored by nonlinear dynamic analysis of the cardiac
    restitution model: the controlled state is confined in a very small region of chaotic attractor in the phase space, resulting in extremely diminished variation in action
    potential durations. This is in contrary to the traditional knowledge in control
    of dynamical systems that chaos should be avoided. Most of our theoretical pre-
    dictions are well verified experimentally in isolated heart rats. Our method is
    much more robust to noise than previous alternans reduction methods based on
    fixed point stabilization and should be more efficient in terms of experimental
    implementation, and thus for potential clinical treatment for arrhythmia.

    1 Introduction 1 1.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1.2 Action Potential Duration Restitution . . . . . . . . . . . . . . . . 4 1.3 Cardiac Ventricular Fibrillation . . . . . . . . . . . . . . . . . . . . 6 1.4 Cardiac Alternans and Its Feedback Controls . . . . . . . . . . . . . 8 2 Predicting Self-terminating Ventricular Fibrillation in an Isolated Heart 12 2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 2.2 Experiments and Raw Data . . . . . . . . . . . . . . . . . . . . . . 14 2.3 Data analysis methods . . . . . . . . . . . . . . . . . . . . . . . . . 18 2.3.1 Fourier Power Spectrum . . . . . . . . . . . . . . . . . . . . 19 2.3.2 Wavelet Power Spectrum . . . . . . . . . . . . . . . . . . . . 21 2.4 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 2.4.1 Wavelet Power Spectrum Results . . . . . . . . . . . . . . . 23 2.4.2 Fourier Power Spectrum . . . . . . . . . . . . . . . . . . . . 26 2.5 Discussions and Summary . . . . . . . . . . . . . . . . . . . . . . . 30 3 Suppression of Cardiac Alternans by T+T-Feedback Control 34 3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 3.2 T+T-feedback control for suppression of alternans . . . . . . . . . 37 3.3 T+T-control in experiments and simulation of iterated map . . . . 38 3.3.1 Experiments on whole isolated rat hearts . . . . . . . . . . . 38 3.3.2 Iterated map simulation . . . . . . . . . . . . . . . . . . . . 40 3.4 Nonlinear dynamic analysis of the T+T-feedback control . . . . . . 43 3.5 Theoretical Results, Experimental Verification and Discussions . . . 48 3.5.1 The critical value of control parameter ǫC . . . . . . . . . . 48 3.5.2 Dynamics of chaotic attractors . . . . . . . . . . . . . . . . . 49 3.5.3 Improvement of control after trapping the system in the chaotic attractor . . . . . . . . . . . . . . . . . . . . . . . . 52 3.5.4 Transient states of the chaotic attractors . . . . . . . . . . . 52 3.5.5 Critical slowing down as ǫ → ǫ+ C . . . . . . . . . . . . . . . . 57 3.5.6 Merging of two chaotic attractors . . . . . . . . . . . . . . . 58 3.6 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 4 Conclusion and Perspective 62 4.1 Prediction of STVF . . . . . . . . . . . . . . . . . . . . . . . . . . . 62 4.2 Control of cardiac alternans and chaos by T+T-. . . . . . . . . . . 65 A Map model of voltage-calcium coupling 69 B Matlab code of T+T-control scheme for APD restitution model 72 Bibliography 75

    [1] E. Sch¨oll and H. G. Schuster, Handbook of Chaos Control, 2nd Edition, 2008.
    [2] M. R. Lauer, Sung R.J. In Podrid, P. J., Kowey,P.R., Cardiac Arrhythmia:
    Mechanisms, Diagnosis, and Management, Lippincott Williams and Wilkins,
    Philadelphia, 2001.
    [3] Karma A. and Gilmore R. F., Nonlinear Dynamics of Heart Rhythm Disor-
    ders, Phys. Today March, 51 (2007).
    [4] Qu Z., and Weiss J. N., Dynamics and Cardiac Arrhythmias, J. Cardiovasc.
    Electr., 17, 1042 (2006).
    [5] E. M. Cherry and F. H. Fenton, Visualization of spiral and scroll waves in
    simulated and experimental cardiac tissue, New J. Phys., 10, 125016, (2008).
    [6] M. L. Koller, M. L. Riccio and R. F. Gilmour, Dynamic Restitution of Action
    Potential Duration During Electrical Alternans and Ventricular Fibrillation,
    Am. J. Physiol. Heart. Circ. Physiol., 275, H1635 (1998).
    [7] Z. Qu, Y. Shiferaw, and J. N. Weiss, Nonlinear Dynamics of Cardiac
    Excitation-Contraction Coupling: an Iterated Map Study, Phys. Rev. E 75,
    011927 (2007).
    [8] Nolasco JB, Dahlen RW, A graphic method for the study of alternation in
    cardiac action potentials, J. Appl. Physiol. 25, 191-196, (1968).
    [9] Chialvo DR, Gilmour RF,Jalife J, it Low dimensional chaos in cardiac tissue,
    Nature, 343, 653-657, (1990).
    [10] J. J. Foxet al., Period-doublinginstability and memoryin cardiac tissue, PRL
    89, 138101 (2002).
    [11] Y. Shiferawet al., Nonlinear dynamics of paced cardiac cells, Ann. N.Y. Acad.
    Sci. 1080, 376-394 (2006).
    [12] Robles de Medina E. O., Bernard R., Coumel P., et. al, Definition of Terms
    Related to Cardiac Rhythm. WHO/ISFC Task Force, Eur. J. Cardiol., 8
    (1978)127
    [13] Wigger C. J., The mechanism andnature of ventricular fibrillation, Am. Heart J., 20 (1940)399.
    [14] Moe GK, On the multiple wavelet hypothesis of atrial fibrillation, Arch. Int.
    Pharmacodyn. Ther., 14,183, 1982.
    [15] Weiss JN et al., The dynamics of cardiac fibrillation, Circulation, 112 1232,
    2005.
    [16] Jalife J, Berenfeld O, Mansour M, Mother rotors and fibrillatory conduction:
    A mechanism of atrial fibrillation, Cardiovasc. Res., 54, 204, 2002
    [17] P. S. Chen et al., A tale of two fibrillations, Circulation, 108 2298, 2003.
    [18] J. Jalife, VENTRICULAR FIBRILLATION: Mechanisms of Initiation and
    Maintenance, Annu. Rev. Physiol. 62, 25, 2000.
    [19] van Hemel N. M. and Kingma J. H., A Patient in Whom Self-terminating
    Ventricular Fibrillation was a Manifestation of Myocardial Reperfusion, Br.
    Heart. J., 69 (1993)568.
    [20] Blaer Y. et. al, Transient Ventricular Fibrillation. A Clinical Case Report,
    Eur. J. Cardiovasc. Nurs., 6, (2007) 337.
    [21] Clayton R. H., Murray A. and Campbell R. W. F., Frequency Analysis of
    Self-terminating Ventricular Fibrillation Computers in Cardiology, (1994)
    705.
    [22] C. Hirth, U. Borchard and , D. Hafner, Effects of the calcium antagonist dilti-azem on action potentials, slow response and force of contraction in different cardiac tissues, J. of Mol. Cell. Card. 15, 799 (1983)
    [23] D. V. Euler, Cardiac alternans: mechanisms and pathophysiological signifi-cance, Cardiovascular Research, 43, 583 (1999)
    [24] Y. Shiferaw, A. Karma, Turing instability mediated by voltage and calcium diffusion in paced cardia ccells, PNAS, 103, 5670, (2006)
    [25] Ott, E., Grebogi, C., and Yorke, J.A, Controlling Chaos, Phys. Rev. Lett. 64,1196 (1990).
    [26] D. J. Christini et. al, Control of electrical alternans in canine cardiac Purkinje fibers, Phys. Rev. Lett. 96, 104101 (2006).
    [27] G. M. Hall and D. J. Gauthier, Experimental control of cardiac muscle alter-nans, Phys. Rev. Lett. 88, 198102 (2002).
    [28] K. Hall et al., Dynamic Control of Cardiac Alternans, Phys. Rev. Lett. 78, 4518 (1997);D. J. Christini et al., Nonlinear-dynamical arrhythmia control in humans, Proc. Nat. Acad. Sci. U.S.A. 98, 5827 (2001).
    [29] B. Echebarria and A. Karma, Spatiotemporal control of cardiac alternans, Chaos 12, 923 (2002)
    [30] D. J. Christini and J. J. Collins, Using chaos control and tracking to suppress a pathological nonchaotic rhythm in a cardiac model, Phys. Rev. E, 53, R49 (1996)
    [31] E. Chudin, J. Goldhaber, A. Garfinkel et al., Intracellular Ca(2+) dynamics and the stability of ventricular tachycardia, Biophys. J., 77, 29302941 (1999)
    [32] Carlos de Diego et al., Spatially discordant alternans in cardiomyocyte mono-layers, Am. J. Physiol. Heart. Circ. Physiol, 294, H1417H1425 (2008)
    [33] G. Yuan, G. Wang and S. Chen, Control of spiral waves and spatiotemporal
    chaos by periodic perturbation near the boundary , Europhys. Lett., 72 (2005)
    908.
    [34] Osipov G. V., Shulgin B. V. and Collins J. J., Controlled movement and
    suppression of spiral waves in excitable media, Phys. Rev. E, 58 (1998)6955.
    [35] Hudgins L., Friehe C. A. and M. E. Mayer, Wavelet transforms and atmo-spheric turbulence, Phys. Rev. Lett., 71 (1993)3279.
    [36] Dvornikov A. V., Mi Y.C. and Chan C. K., Transient Analysis of ForceFre-
    quency Relationships in Rat Hearts Perfused by Krebs-Henseleit and Tyrode
    Solutions with Different [Ca2+]o, Cardiovasc. Eng. Tech., 3 (2012)203
    [37] Sridhar S. , Le D.M., MiY.C., Sinha S., LaiP.Y., andChan C.K., Suppression
    of cardiac alternans by alternating-period-feedback stimulations, Phys. Rev. E,
    87, (2013) 042712 .
    [38] D. M. Le, Alexey V. Dvornikov, Pik-Yin Lai, and C. K. Chan Predicting self-
    terminating ventricular fibrillations in an isolated heart, EPL, 104, 48002
    (2013)
    [39] National Research Council, Guide for the care and use of laboratory animals,
    Washington, DC: National Academy Press, 2011.
    [40] Bracewell R. N., The fourier transform and its applications,3rd Edition (Mc-
    Graw Hill, Boston) 2000.
    [41] Grinsted A., Moore J. C. and Jevrejeva S., Application of the cross wavelet
    transform and wavelet coherence to geophysical time series, Nonlinear Proc.
    Geoph., 11 (2004)561.
    [42] Grinsted A., Moore J. C. and Jevrejeva S., Matlab software pack-
    age for performing wavelet and cross wavelet transform, noc.ac.uk/using-
    science/crosswavelet-wavelet-coherence
    [43] Maraun D. andKurths J., Holschneider M.,NonstationaryGaussian processes
    in wavelet domain: synthesis, estimation, and significance testing, Phys. Rev.
    E, 75 (2007)016707.
    [44] Ivanov P.C. etal., Scalingbehaviour of heartbeat intervals obtained by wavelet-
    based time-series analysis, Nature 383 (1996) 323; Scaling and universality
    in heart rate variability distributions, Physica A 249 (1998)587.
    [45] Ivanov P.C. et al., From 1/f Noise to Multifractal Cascades in Heartbeat
    Dyamics, Chaos 11 (2001)641.
    [46] Kamkin A., Kiseleva I., Isenberg G. et al., Cardiac fibroblasts and the
    mechano-electric feedback mechanism in healthy and diseased hearts, Prog.
    Biophys. Mol. Biol., 82 (2003)111.
    [47] Horner S. M., Murphy C. F., Coen B. et al., Contribution to heart rate vari-
    abilityby mechanoelectric feedback. Stretch of the sinoatrial node reduces heart
    rate variability, Circulation, 94(1996)1762.
    [48] Biktashev V. N, Dissipation of the excitation wave fronts, Phys. Rev. Lett.
    89 (2002)168102; Aslanidi O. V., Bailey A., Biktashev V. N, Clayton R. H.
    and Holden A. V., Enhanced self-termination of re-entrant arrhythmias as a
    pharmacological strategy for antiarrhythmic action, Chaos, 12 (2002)843.
    [49] Biktasheva I. V., Biktashev V. N., Dawes W. N., Holden A. V., Saumarez
    R. C. and Savill A. M., Dissipation of the excitation front as a mechanism of
    self-terminating arrhythmias, Int. J. Bifurcat. Chaos, 13 (2003)3645.
    [50] Biktasheva I. V., Biktashev V. N. and Holden A. V., Wavebreaks and self-
    termination of spiral waves in a model of human atrial tissue, FIMH, 3504
    (2005)293.
    [51] Armstrong C. M. and Cota G., PNAS, Calcium block of Na+ channels and
    its effect on closing rate, 96 (1999)4154.
    [52] de la Casa et al., Spiral wave annihilation by low-frequency planar fronts in a
    model of excitable media, Euophys. Lett. 86 (2009)18005; Patterns of spiral
    wave attenuation by low-frequency periodic planar fronts., Chaos 17 (2007)
    015109.
    [53] Fisher, J. D., R. Mehra, et al., Termination of ventricular tachycardia with
    bursts of rapid ventricular pacing, Am. J. Card. 41, 94 (1978)
    [54] A. Pumir, S. Sinha, S. Sridhar, M. Argentina, M. Horning, S. Filippi, C.
    Cherubini, S. Luther and V. Krinsky, Wave-train-induced termination of
    weakly anchored vortices in excitable media, Phys. Rev. E 81, 010901 (2010)
    [55] J. M. Cao, Z. L. Qu, et al., Spatiotemporal heterogeneity in the induction
    of ventricular fibrillation by rapid pacing: importance of cardiac restitution
    properties, Circ. Res. 84, 1318 (1999)
    [56] J. Breuer andS. Sinha, Death, dynamics and disorder: Terminatingreentryin
    excitable media by dynamically induced inhomogeneities, Pramana: J. Phys.
    64, 553 (2005)
    [57] D. J. Gauthier andJ.E.S. Socolar, Comment on “Dynamic Control of Cardiac
    Alternans”, Phys. Rev. Lett. 79, 4938 (1997).
    [58] K. Hall, D. J. Christini, M. Tremblay, J. J. Collins, L. Glass and J. Billette,
    Dynamic Control of Cardiac Alternans, Phys. Rev. Lett. 78, 4518 (1997)
    [59] J. N. Weiss, M. Nivala, A. Garfinkel, and Z. Qu, Alternans and arrhythmias:
    from cell to heart, Circ. Res. 108, 98 (2011).
    [60] M. R. Boyett and B. R. Jewell, A study of the factors responsible for rate-
    dependent shortening of the action potential in mammalian ventricular mus-
    cle, J. Physio. (Lond.) 285, 359 (1978).
    [61] E.G. Tolkacheva et. al, Analysis of the Fenton-Karma model through aproxi-
    mation by a one-dimensional map, Chaos 12, 1034 (2002).
    [62] C. H. Luo and Y. Rudy, A model of the ventricular cardiac action potential.
    Depolarization, repolarization, and their interaction, Circ. Res., 68 , 1501
    (1991).
    [63] B. Echebarria and A. Karma, Instability and Spatiotemporal Dynamics of
    Alternans in Paced Cardiac Tissue Phys. Rev. Lett. 88, 208101 (2002).
    [64] Hila Dvir and Sharon Zlochiver, Stochastic Cardiac Pacing Increases Ven-
    tricular Electrical StabilityA Computational Study, Biophysical Journal, 105
    ,533542, 2013.

    QR CODE
    :::