Spiral wave reentry as a mechanism of lethal ventricular arrhythmias has been widely demonstrated in animal experiments and recordings from human hearts. It has been shown that in structurally normal hearts, spiral waves are unstable, breaking up into multiple wavelets via dynamical instabilities. However, many of the second-generation action potential models give rise only to stable spiral waves, raising issues regarding the underlying mechanisms of spiral wave breakup. In this study, we carried out computer simulations of two-dimensional homogeneous tissues using five ventricular action potential models. We show that the transient outward potassium current (I_to), although it is not required, plays a key role in promoting spiral wave breakup in all five models. As the maximum conductance of I_to increases, it first promotes spiral wave breakup and then stabilizes the spiral waves. In the absence of I_to, speeding up the L-type calcium kinetics can prevent spiral wave breakup, however, with the same speedup kinetics, spiral wave breakup can be promoted by increasing I_to. Increasing I_to promotes single-cell dynamical instabilities, including action potential duration alternans and chaos, and increasing I_to further suppresses these action potential dynamics. These cellular properties agree with the observation that increasing I_to first promotes spiral wave breakup and then stabilizes spiral waves in tissue. Implications of our observations to spiral wave dynamics in the real hearts and action potential model improvements are discussed.

中文翻译：

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瞬时外向钾电流在心室组织螺旋波破裂中起关键作用


螺旋波折返作为致命性室性心律失常的一种机制已在动物实验和人类心脏记录中得到广泛证明。研究表明，在结构正常的心脏中，螺旋波不稳定，通过动态不稳定性分解成多个小波。然而，许多第二代动作电位模型仅产生稳定的螺旋波，引发了有关螺旋波破裂的潜在机制的问题。在这项研究中，我们使用五个心室动作电位模型对二维均质组织进行了计算机模拟。我们表明，瞬态向外钾电流 (I _to ) 尽管不是必需的，但在所有五个模型中都在促进螺旋波破碎中发挥着关键作用。随着I _to最大电导的增加，它首先促进螺旋波的破碎，然后稳定螺旋波。在没有 I _to的情况下，加速 L 型钙动力学可以防止螺旋波破碎，然而，在相同的加速动力学下，增加 I _to可以促进螺旋波破碎。增加 I_可促进单细胞动态不稳定性，包括动作电位持续时间交替和混乱，增加 I_可进一步抑制这些动作电位动态。这些细胞特性与增加 I_首先促进螺旋波破裂然后稳定组织中螺旋波的观察结果一致。讨论了我们的观察结果对真实心脏中螺旋波动力学的影响以及动作电位模型的改进。