Alternans and spiral breakup in a human ventricular tissue model
Alternans and spiral breakup in a human ventricular tissue model
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DOI：
10.1152/ajpheart.00109.2006
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发表时间：
2006-09-01
影响因子：
4.8
通讯作者：
Panfilov, A. V.
中科院分区：
文献类型：
--
作者：
ten Tusscher, K. H. W. J.;Panfilov, A. V.
室颤(VF)是西方世界的主要死亡原因之一。根据一种假说，室颤时的混沌兴奋动力学是动作电位时程动态不稳定性的结果，这种不稳定性的发生需要动作电位时程恢复曲线的斜率大于1。电紧张性耦合和心脏记忆等其他因素也决定了这些不稳定性的发生。在本文中，我们研究了人体心脏组织中交替和螺旋破裂的条件。因此，我们开发了一种新的人类心室肌细胞模型，该模型基于最近对人体动作电位恢复的实验测量，并包括对细胞内钙动力学的更广泛的描述。我们应用这个模型来研究单个细胞中的电不稳定性、细胞环中的折返波以及二维室组织片中的折返波的条件。我们发现，快钠流的恢复动力学是导致不稳定性开始的一个重要因素。钠电流恢复越慢，螺旋波的旋转周期越长，传导速度恢复越缓慢，这两者都抑制了恢复介导的不稳定性。因此，最大恢复坡度可能远远超过1(最高1.5)，才会发生电气不稳定。虽然我们研究中发现的失稳发生所需的坡度超过1，但它们在实验测量的坡度范围内。因此，我们得出结论，陡峭的动作电位恢复介导的不稳定性是人类心脏室颤的一种潜在机制。
Ventricular fibrillation (VF) is one of the main causes of death in the Western world. According to one hypothesis, the chaotic excitation dynamics during VF are the result of dynamical instabilities in action potential duration (APD) the occurrence of which requires that the slope of the APD restitution curve exceeds 1. Other factors such as electrotonic coupling and cardiac memory also determine whether these instabilities can develop. In this paper we study the conditions for alternans and spiral breakup in human cardiac tissue. Therefore, we develop a new version of our human ventricular cell model, which is based on recent experimental measurements of human APD restitution and includes a more extensive description of intracellular calcium dynamics. We apply this model to study the conditions for electrical instability in single cells, for reentrant waves in a ring of cells, and for reentry in two-dimensional sheets of ventricular tissue. We show that an important determinant for the onset of instability is the recovery dynamics of the fast sodium current. Slower sodium current recovery leads to longer periods of spiral wave rotation and more gradual conduction velocity restitution, both of which suppress restitution-mediated instability. As a result, maximum restitution slopes considerably exceeding 1 (up to 1.5) may be necessary for electrical instability to occur. Although slopes necessary for the onset of instabilities found in our study exceed 1, they are within the range of experimentally measured slopes. Therefore, we conclude that steep APD restitution-mediated instability is a potential mechanism for VF in the human heart.