The role of cardiac tissue alignment in modulating electrical function
The role of cardiac tissue alignment in modulating electrical function
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DOI：
10.1111/j.1540-8167.2007.00959.x
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发表时间：
2007-12-01
影响因子：
2.7
通讯作者：
Entcheva, Emilia
中科院分区：
文献类型：
--
作者：
Chung, Chiung-Yin;Bien, Harold;Entcheva, Emilia
心脏组织的排列和功能。导言：大多数心律失常都与病理触发的离子通道重构有关。然而，多细胞效应，例如，夸大各向异性和改变细胞间的耦合，也可以通过改变电张力来间接影响动作电位的形态和电稳定性。这些变化与结构性心脏病尤其相关，包括肥厚和脑梗塞。最近的计算研究表明，电张力通过改变动力学性质(恢复)来影响稳定性。我们通过实验解决了细胞排列和连通性如何改变组织功能以及这些影响是否依赖于波传播方向的问题。方法和结果：我们表明，在体外心脏组织模型中，心脏细胞排列可以通过依赖和不依赖于波传播方向的机制来改变电稳定性，并且局部结构重构可以被感觉到超出空间常数。值得注意的是，动作电位时程和传导速度的恢复沿细胞排列方向明显变陡。此外，在高度各向异性的细胞网络中，无论是纵向还是横向传播，都发现动作电位时程和钙瞬变持续时间延长。这与仅基于电张力效应的波传播方向和动作电位的预期相关性相反，但与我们的发现一致，即在排列的结构中，细胞大小增加，心钠素(一种肥大标志物)的分泌增加。结论：各向异性结构是通过电张力和分子信号调节电稳定性的有效调节器。在心律失常发生的实验和计算模型中以及在设计有效的治疗方法时，必须考虑组织对齐。
Cardiac Tissue Alignment and Function. Introduction: Most cardiac arrhythmias are associated with pathology-triggered ion channel remodeling. However, multicellular effects, for example, exaggerated anisotropy and altered cell-to-cell coupling, can also indirectly affect action potential morphology and electrical stability via changed electrotonus. These changes are particularly relevant in structural heart disease, including hypertrophy and infarction. Recent computational studies showed that electrotonus factors into stability by altering dynamic properties (restitution). We experimentally address the question of how cell alignment and connectivity alter tissue function and whether these effects depend on the direction of wave propagation.Methods and Results: We show that cardiac cell arrangement can alter electrical stability in an in vitro cardiac tissue model by mechanisms both dependent and independent of the direction of wave propagation, and local structural remodeling can be felt beyond a space constant. Notably, restitution of action potential duration (APD) and conduction velocity was significantly steepened in the direction of cell alignment. Furthermore, prolongation of APD and calcium transient duration was found in highly anisotropic cell networks, both for longitudinal and transverse propagation. This is in contrast to expected correlation between wave propagation direction and APD based on electrotonic effects only, but is consistent with our findings of increased cell size and secretion of atrial natriuretic factor, a hypertrophy marker, in the aligned structures.Conclusion: Our results show that anisotropic structure is a potent modulator of electrical stability via electrotonus and molecular signaling. Tissue alignment must be taken into account in experimental and computational models of arrhythmia generation and in designing effective treatment therapies.