Scroll-Wave Dynamics in Human Cardiac Tissue: Lessons from a Mathematical Model with Inhomogeneities and Fiber Architecture

Cardiac arrhythmias, such as ventricular tachycardia (VT) and ventricular fibrillation (VF), are among the leading causes of death in the industrialized world. These are associated with the formation of spiral and scroll waves of electrical activation in cardiac tissue; single spiral and scroll waves are believed to be associated with VT whereas their turbulent analogs are associated with VF. Thus, the study of these waves is an important biophysical problem. We present a systematic study of the combined effects of muscle-fiber rotation and inhomogeneities on scroll-wave dynamics in the TNNP (ten Tusscher Noble Noble Panfilov) model for human cardiac tissue. In particular, we use the three-dimensional TNNP model with fiber rotation and consider both conduction and ionic inhomogeneities. We find that, in addition to displaying a sensitive dependence on the positions, sizes, and types of inhomogeneities, scroll-wave dynamics also depends delicately upon the degree of fiber rotation. We find that the tendency of scroll waves to anchor to cylindrical conduction inhomogeneities increases with the radius of the inhomogeneity. Furthermore, the filament of the scroll wave can exhibit drift or meandering, transmural bending, twisting, and break-up. If the scroll-wave filament exhibits weak meandering, then there is a fine balance between the anchoring of this wave at the inhomogeneity and a disruption of wave-pinning by fiber rotation. If this filament displays strong meandering, then again the anchoring is suppressed by fiber rotation; also, the scroll wave can be eliminated from most of the layers only to be regenerated by a seed wave. Ionic inhomogeneities can also lead to an anchoring of the scroll wave; scroll waves can now enter the region inside an ionic inhomogeneity and can display a coexistence of spatiotemporal chaos and quasi-periodic behavior in different parts of the simulation domain. We discuss the experimental implications of our study.心脏心律失常（Cardiac arrhythmias），如室性心动过速（ventricular tachycardia, VT）与心室颤动（ventricular fibrillation, VF），是工业化国家最主要的致死病因之一。此类病症与心脏组织内电激活螺旋波与卷轴波（spiral and scroll waves）的形成紧密相关；学界普遍认为，单一螺旋波与卷轴波与室性心动过速相关，而其湍流态类似物则与心室颤动相关。因此，对这类电波的研究是一项重要的生物物理课题。 本研究针对人类心脏组织的TNNP（ten Tusscher Noble Noble Panfilov）模型，系统探究了肌纤维旋转与非均匀性的联合作用对卷轴波动力学的影响。具体而言，我们采用包含肌纤维旋转的三维TNNP模型，同时考量传导性与离子性非均匀性两类因素。 研究发现，卷轴波动力学不仅对非均匀性的位置、尺寸与类型存在敏感依赖性，同时也与肌纤维旋转程度密切相关。我们观察到，卷轴波锚定至圆柱形传导非均匀性的倾向随非均匀体半径增大而增强。此外，卷轴波的丝状体可表现出漂移或蜿蜒、跨壁弯曲、扭曲以及破裂现象。 若卷轴波丝状体呈现弱蜿蜒行为，则该波在非均匀体处的锚定效应与肌纤维旋转对波钉扎（wave-pinning）的破坏效应之间会达到精细平衡；若该丝状体呈现强蜿蜒行为，则锚定效应同样会被肌纤维旋转抑制，此时卷轴波可从大部分心肌层中消失，仅能通过种子波（seed wave）重新生成。 离子性非均匀性同样可引发卷轴波的锚定；此时卷轴波可进入离子性非均匀体内部区域，并在模拟域的不同区域同时表现出时空混沌与准周期行为。最后，我们讨论了本研究的实验启示。