Dipartimento di Matematica, Università di Pavia, Via Ferrata 1, Pavia, Italy.
Math Biosci. 2011 Apr;230(2):96-114. doi: 10.1016/j.mbs.2011.02.002. Epub 2011 Feb 15.
Published studies have investigated the relevance of cardiac virtual electrode responses to unipolar cathodal and anodal stimulations for explaining the make and break excitation mechanisms. Most of these studies have considered 2D bidomain models or cylindrical domains that by symmetry reduce to the 2D case, so the triggering mechanisms and onset of excitation have not yet been fully elucidated in 3D anisotropic models. The goal of this work is to revisit these excitation mechanisms with 3D bidomain simulations considering two tissue types with unequal anisotropy ratio, including transmural fiber rotation and augmenting the Luo-Rudy I membrane model with the so-called funny and the electroporation currents. In addition to usual snapshots of transmembrane potential patterns, we compute from the action potential waveforms the activation time and associated isochrone sequences, yielding a detailed 3D description of the instant and location of excitation origin, shape and propagation of activation wavefronts. A specific aim of this work is to detect the location of the excitation onset and whether its trigger mechanism is (a) electrotonic, i.e. originating from discharge diffusion of currents flowing between virtual cathodes and anodes and/or (b) membrane-based, i.e. arising only from intrinsic depolarizing membrane currents. Our results show that the electrotonic mechanism is observed independently of the degree of unequal anisotropy in diastolic anode make and systolic cathode break. The membrane-based mechanism is observed in diastolic cathode make, diastolic anode break, only for a relative weak anisotropy, and systolic anode break. The excitation trigger mechanism, the location of the excitation origin and the pattern of the isochrone sequence are independent of the degree of anisotropy for diastolic cathode make, systolic cathode and anode break, while they might depend on the degree of anisotropy for diastolic anode make and break. Moreover, the tissue anisotropy has a strong influence on the threshold amplitude of the stimulation pulse triggering these mechanisms.
已发表的研究调查了心脏虚拟电极对单极阴极和阳极刺激的反应与解释产生和中断兴奋机制的相关性。这些研究大多考虑了 2D 双域模型或圆柱域，这些模型通过对称简化为 2D 情况，因此在 3D 各向异性模型中，触发机制和兴奋起始尚未得到充分阐明。这项工作的目的是通过考虑两种具有不等各向异性比的组织类型的 3D 双域模拟来重新研究这些兴奋机制，包括跨壁纤维旋转，并在用所谓的有趣和电穿孔电流增强 Luo-Rudy I 膜模型。除了通常的跨膜电位模式快照外，我们还从动作电位波形计算激活时间和相关等时序列，从而对兴奋起源的瞬间和位置、激活波阵面的形状和传播进行详细的 3D 描述。这项工作的一个具体目标是检测兴奋起始的位置及其触发机制是(a)电紧张的，即起源于虚拟阴极和阳极之间流动的电流的放电扩散，还是(b)基于膜的，即仅源于内在去极化膜电流。我们的结果表明，电紧张机制独立于舒张期阳极产生和收缩期阴极中断的各向异性程度而被观察到。基于膜的机制仅在舒张期阴极产生、舒张期阳极中断、相对较弱的各向异性和收缩期阳极中断时被观察到。兴奋触发机制、兴奋起源的位置和等时序列模式独立于舒张期阴极产生、收缩期阴极和阳极中断的各向异性程度，而它们可能依赖于舒张期阳极产生和中断的各向异性程度。此外，组织各向异性对触发这些机制的刺激脉冲的阈值幅度有很强的影响。
