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人类心室组织中波斑图引起的后除极化研究

王小艳 汪芃 唐国宁

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人类心室组织中波斑图引起的后除极化研究

王小艳, 汪芃, 唐国宁

Afterdepolarlizations induced by wave pattern in human ventricular tissue

Wang Xiao-Yan, Wang Peng, Tang Guo-Ning
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  • 突然的心脏死亡常常由心脏的心律失常引起,而心律失常常与后除极化有关.本文采用人类心脏模型研究了二维心肌组织中存在螺旋波或其他波斑图下后除极化的发生,通过改变L型钙电导和快钾电导让螺旋波演化,观察后除极化在空间的分布.研究发现:在单细胞和一维情况下不出现后除极化时,螺旋波可导致相II型和相III型早期后除极化、延迟后除极化、增强的自动性,以及延时激发和延时增强自动性的出现;还观察到螺旋波导致膜电位在动作电位I期出现弱振荡;后除极化一般出现在螺旋波波核区域,它是由螺旋波的相奇异点引起.后除极化也可以分布在更大的范围,当参数选取适当时,出现早期后除极化、延迟后除极化、增强自动性的空间点在空间呈螺旋线分布,展示记忆效应.通过观察各种离子电流变化发现:当激发细胞的钠电流很小时可诱发L型钙电流、钠钙交换电流的增大和慢钾电流、快钾电流的减少,导致各种后除极化的产生,因此增大钠电流可有效抑制后除极化的发生.
    Recently, arrhythmogenic condition has attracted special attention of scientists in the field of different disciplines because sudden cardiac death is often caused by cardiac arrhythmia. Arrhythmias can have different underlying causes. But the underlying mechanism of arrhythmia is not fully understood due to cardiac complexity. As is well known, one particular group of arrhythmias is often associated with the afterdepolarizations. So far, afterdepolarizations have been studied mainly in isolated cardiac cells. The question how the afterdepolarization is produced at a tissue level has not been widely studied yet. In this paper, we use the model of human heart to study how spiral wave or other wave patterns induces the afterdepolarizations in two-dimensional myocardial tissue. We try to obtain the instantaneous spatial distribution of afterdepolarizations by changing the L-type calcium and fast potassium conductance. In order to avoid bringing in afterdepolarizations, the applied parameters avoid evoking the afterdepolarizations at a single-cell and one-dimensional tissues level. The numerical simulation results show that spiral wave and other wave patterns can cause the phase II and III early afterdepolarizations, the delayed afterdepolarization, the enhanced automaticity, the delayed excitation and the delayed enhanced automaticity to occur. Moreover, we observe the weak oscillation of the membrane potential during the phase I of action potential. The afterdepolarizations generally occur in the spiral-wave core. They are generated by the phase singularity of spiral wave. The afterpolarizations can also appear in other region of spiral wave pattern. The afterpolarization is characterized by scattered distribution. When parameters are appropriately chosen, we observe the outbreaks of different afterpolarizations under the state of spiral wave. The corresponding spatial and temporal distributions of the early afterdepolarizations, the delayed afterdepolarizations, and the enhanced automaticity become spiral line distributions, which exhibits memory effect. It is shown that the outbreaks of afterdepolarizations in the system do not necessarily lead to the breakup of spiral wave. By observing the changes of different ion currents we find that when sodium current exciting cell is very small, the weak excitation with small sodium current can cause the L-type calcium current and the sodium calcium exchange current to increase, and the slow potassium current and rapid potassium current to decrease, leading to the occurrences of various afterdepolarizations. Therefore, increasing sodium current can effectively suppress the occurrences of afterdepolarizations.
      通信作者: 唐国宁, tangguoning@sohu.com
    • 基金项目: 国家自然科学基金(批准号:11565005,11365003)资助的课题.
      Corresponding author: Tang Guo-Ning, tangguoning@sohu.com
    • Funds: Project supported by the National Natural Science Foundation of China (Grant Nos. 11565005, 11365003).
    [1]

    Gray R A, Jalife J, Panfilov A, Baxter W T, Cabo C, Davidenko J M, Pertsov A M 1995 Circulation 91 2454

    [2]

    Fenton F H, Cherry E M, Hastings H M, Evans S J 2002 Chaos 12 852

    [3]

    Ouyan Q 2001 Physics 30 30 (in Chinese) [欧阳颀 2001 物理 30 30]

    [4]

    Keldermann R H, Ten Tusscher K H W J, Nash M P, Bradley C P, Hren R, Taggart P, Panfilov A V 2009 Am. J. Physiol. Heart Circ. Physiol. 296 H370

    [5]

    Qu Z, Xie F, Garfinkel A, Weiss J N 2000 Ann. Biomed. Eng. 28 755

    [6]

    Courtemanche M 1996 Chaos 6 579

    [7]

    Shajahan T K, Nayak A R, Pandit R 2009 PLoS One 4 e4738

    [8]

    Kazbanov I V, Clayton R H, Nash M P, Bradley C P, Paterson D J, Hayward M P, Taggart P, Panfilov A V 2014 PLoS Comput. Biol. 10 e1003891

    [9]

    Priebe L, Beuckelmann D J 1998 Circ. Res. 82 1206

    [10]

    Ten Tusscher K H W J, Noble D, Noble P J, Panfilov A V 2004 Am. J. Physiol. Heart Circ. Physiol. 286 H1573

    [11]

    Iyer V, Mazhari R, Winslow R L 2004 Biophys. J. 87 1507

    [12]

    Grandi E, Pasqualini F S, Bers D M 2010 J. Mol. Cell Cardiol. 48 112

    [13]

    O'Hara T, Virg L, Varr A, Rudy Y 2011 PLoS Comput. Biol. 7 e1002061

    [14]

    Ten Tusscher K H W J, Hren R, Panfilov A V 2007 Circ. Res. 100 e87

    [15]

    Zimik S, Vandersickel N, Nayak A R, Panfilov A V, Pandit R 2015 PLoS One 10 e0130632

    [16]

    de Ferrari G M, Viola M, D'Amato E, Antolini R, Forti S 1995 Circulation 91 2510

    [17]

    Xie L H, Chen F, Karagueuzian H S, Weiss J N 2009 Circ. Res. 104 79

    [18]

    Karagueuzian H S, Nguyen T P, Qu Z, Weiss J N 2013 Front. Physiol. 4 1

    [19]

    Schillinger K J, Patel V V 2012 J. Geriatr. Cardiol. 9 379

    [20]

    Zhao Z, Wen H, Fefelova N, Allen C, Baba A, Matsuda T, Xie L H 2012 Am. J. Physiol. Heart Circ. Physiol. 302 H1636

    [21]

    Sato D, Xie L H, Nguyen T P, Weiss J N, Qu Z 2010 Biophys. J. 99 765

    [22]

    Vandersickel N, Kazbanov I V, Nuitermans A, Weise L D, Pandit R, Panfilov A V 2014 PLoS One 9 e84595

    [23]

    Liu M B, de Lange E, Garfinkel A, Weiss J N, Qu Z 2015 Heart Rhythm 12 2115

    [24]

    Martens E A, Laing C R, Strogatz S H 2010 Phys. Rev. Lett. 104 044101

    [25]

    Walker R G, Koster R W, Sun C, Moffat G, Barger J, Dodson P P, Chapman F W 2009 Resuscitation 80 773

  • [1]

    Gray R A, Jalife J, Panfilov A, Baxter W T, Cabo C, Davidenko J M, Pertsov A M 1995 Circulation 91 2454

    [2]

    Fenton F H, Cherry E M, Hastings H M, Evans S J 2002 Chaos 12 852

    [3]

    Ouyan Q 2001 Physics 30 30 (in Chinese) [欧阳颀 2001 物理 30 30]

    [4]

    Keldermann R H, Ten Tusscher K H W J, Nash M P, Bradley C P, Hren R, Taggart P, Panfilov A V 2009 Am. J. Physiol. Heart Circ. Physiol. 296 H370

    [5]

    Qu Z, Xie F, Garfinkel A, Weiss J N 2000 Ann. Biomed. Eng. 28 755

    [6]

    Courtemanche M 1996 Chaos 6 579

    [7]

    Shajahan T K, Nayak A R, Pandit R 2009 PLoS One 4 e4738

    [8]

    Kazbanov I V, Clayton R H, Nash M P, Bradley C P, Paterson D J, Hayward M P, Taggart P, Panfilov A V 2014 PLoS Comput. Biol. 10 e1003891

    [9]

    Priebe L, Beuckelmann D J 1998 Circ. Res. 82 1206

    [10]

    Ten Tusscher K H W J, Noble D, Noble P J, Panfilov A V 2004 Am. J. Physiol. Heart Circ. Physiol. 286 H1573

    [11]

    Iyer V, Mazhari R, Winslow R L 2004 Biophys. J. 87 1507

    [12]

    Grandi E, Pasqualini F S, Bers D M 2010 J. Mol. Cell Cardiol. 48 112

    [13]

    O'Hara T, Virg L, Varr A, Rudy Y 2011 PLoS Comput. Biol. 7 e1002061

    [14]

    Ten Tusscher K H W J, Hren R, Panfilov A V 2007 Circ. Res. 100 e87

    [15]

    Zimik S, Vandersickel N, Nayak A R, Panfilov A V, Pandit R 2015 PLoS One 10 e0130632

    [16]

    de Ferrari G M, Viola M, D'Amato E, Antolini R, Forti S 1995 Circulation 91 2510

    [17]

    Xie L H, Chen F, Karagueuzian H S, Weiss J N 2009 Circ. Res. 104 79

    [18]

    Karagueuzian H S, Nguyen T P, Qu Z, Weiss J N 2013 Front. Physiol. 4 1

    [19]

    Schillinger K J, Patel V V 2012 J. Geriatr. Cardiol. 9 379

    [20]

    Zhao Z, Wen H, Fefelova N, Allen C, Baba A, Matsuda T, Xie L H 2012 Am. J. Physiol. Heart Circ. Physiol. 302 H1636

    [21]

    Sato D, Xie L H, Nguyen T P, Weiss J N, Qu Z 2010 Biophys. J. 99 765

    [22]

    Vandersickel N, Kazbanov I V, Nuitermans A, Weise L D, Pandit R, Panfilov A V 2014 PLoS One 9 e84595

    [23]

    Liu M B, de Lange E, Garfinkel A, Weiss J N, Qu Z 2015 Heart Rhythm 12 2115

    [24]

    Martens E A, Laing C R, Strogatz S H 2010 Phys. Rev. Lett. 104 044101

    [25]

    Walker R G, Koster R W, Sun C, Moffat G, Barger J, Dodson P P, Chapman F W 2009 Resuscitation 80 773

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出版历程
  • 收稿日期:  2016-10-10
  • 修回日期:  2016-11-27
  • 刊出日期:  2017-03-05

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