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Human cardiac systems electrophysiology and arrhythmogenesis: iteration of experiment and computation

机译:人心脏系统电生理学和心律失常:实验和计算的迭代

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摘要

Human cardiac electrophysiology (EP) is a unique system for computational modelling at multiple scales. Due to the complexity of the cardiac excitation sequence, coordinated activity must occur from the single channel to the entire myocardial syncytium. Thus, sophisticated computational algorithms have been developed to investigate cardiac EP at the level of ion channels, cardiomyocytes, multicellular tissues, and the whole heart. Although understanding of each functional level will ultimately be important to thoroughly understand mechanisms of physiology and disease, cardiac arrhythmias are expressly the product of cardiac tissue—containing enough cardiomyocytes to sustain a reentrant loop of activation. In addition, several properties of cardiac cellular EP, that are critical for arrhythmogenesis, are significantly altered by cell-to-cell coupling. However, relevant human cardiac EP data, upon which to develop or validate models at all scales, has been lacking. Thus, over several years, we have developed a paradigm for multiscale human heart physiology investigation and have recovered and studied over 300 human hearts. We have generated a rich experimental dataset, from which we better understand mechanisms of arrhythmia in human and can improve models of human cardiac EP. In addition, in collaboration with computational physiologists, we are developing a database for the deposition of human heart experimental data, including thorough experimental documentation. We anticipate that accessibility to this human heart dataset will further human EP computational investigations, as well as encourage greater data transparency within the field of cardiac EP.
机译:人心脏电生理学(EP)是用于多尺度计算建模的独特系统。由于心脏激发序列的复杂性,必须从单个通道到整个心肌合胞发生协调的活动。因此,已经开发出复杂的计算算法来研究离子通道,心肌细胞,多细胞组织和整个心脏水平的心脏EP。尽管对每个功能水平的理解对于彻底了解生理和疾病的机制最终至关重要,但是心律不齐显然是心脏组织的产物,其包含足够的心肌细胞来维持激活的折返循环。另外,通过心室耦合显着改变了对于心律失常至关重要的心脏细胞EP的几种特性。但是,缺乏相关的人类心脏EP数据,无法在其上开发或验证各种规模的模型。因此,在过去的几年中,我们开发了一种用于多尺度人类心脏生理学研究的范例,并且已经恢复并研究了300多种人类心脏。我们已经生成了丰富的实验数据集,从中我们可以更好地了解人类心律不齐的机制,并可以改善人类心脏EP的模型。此外,我们与计算生理学家合作,正在开发一个用于存放人类心脏实验数据的数据库,其中包括详尽的实验文档。我们预计对人类心脏数据集的可访问性将进一步促进人类EP计算研究,并鼓励在心脏EP领域内提高数据透明度。

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