Centre for Condensed Matter Theory, Department of Physics, Indian Institute of Science, Bangalore, India.
Laboratory for Fluid Physics, Pattern Formation and Biocomplexity, Max Planck Institute for Dynamics and Self-Organization, Göttingen, Germany.
PLoS One. 2020 Mar 13;15(3):e0230214. doi: 10.1371/journal.pone.0230214. eCollection 2020.
Several pathological conditions introduce spatial variations in the electrical properties of cardiac tissue. These variations occur as localized or distributed gradients in ion-channel functionality over extended tissue media. Electrical waves, propagating through such affected tissue, demonstrate distortions, depending on the nature of the ionic gradient in the diseased substrate. If the degree of distortion is large, reentrant activity may develop, in the form of rotating spiral (2d) and scroll (3d) waves of electrical activity. These reentrant waves are associated with the occurrence of lethal cardiac rhythm disorders, known as arrhythmias, such as ventricular tachycardia (VT) and ventricular fibrillation (VF), which are believed to be common precursors of sudden cardiac arrest. By using state-of-the-art mathematical models for generic, and ionically-realistic (human) cardiac tissue, we study the detrimental effects of these ionic gradients on electrical wave propagation. We propose a possible mechanism for the development of instabilities in reentrant wave patterns, in the presence of ionic gradients in cardiac tissue, which may explain how one type of arrhythmia (VT) can degenerate into another (VF). Our proposed mechanism entails anisotropic reduction in the wavelength of the excitation waves because of anisotropic variation in its electrical properties, in particular the action potential duration (APD). We find that the variation in the APD, which we induce by varying ion-channel conductances, imposes a spatial variation in the spiral- or scroll-wave frequency ω. Such gradients in ω induce anisotropic shortening of wavelength of the spiral or scroll arms and eventually leads to instabilitites.
几种病理状况会导致心脏组织的电特性出现空间变化。这些变化表现为离子通道功能在扩展组织介质中的局部或分布式梯度。电脉冲在通过受影响的组织时会发生变形,具体取决于病变基质中离子梯度的性质。如果变形程度较大,可能会出现折返活动,表现为旋转螺旋(2d)和涡旋(3d)电活动波。这些折返波与致命性心律失常的发生有关,如室性心动过速(VT)和心室颤动(VF),它们被认为是心搏骤停的常见前兆。通过使用通用的、离子逼真(人类)心脏组织的最新数学模型,我们研究了这些离子梯度对电脉冲传播的有害影响。我们提出了一种可能的机制,用于解释在心脏组织存在离子梯度的情况下折返波模式的不稳定性的发展,这可能解释了一种心律失常(VT)如何演变为另一种心律失常(VF)。我们提出的机制涉及由于电特性的各向异性变化,特别是动作电位持续时间(APD),导致激励波的波长各向异性减小。我们发现,通过改变离子通道电导来诱导 APD 的变化,会在螺旋波或涡旋波的频率 ω 中产生空间变化。这种 ω 的梯度会导致螺旋或涡旋臂的波长各向异性缩短,最终导致不稳定性。