Abstract
Pacemaking dysfunction has become a significant disease that may contribute to heart rhythm disorders, syncope, and even death. Up to now, the best way to treat it is to implant electronic pacemakers. However, these have many disadvantages such as limited battery life, infection, and fixed pacing rate. There is an urgent need for a biological pacemaker (bio-pacemaker). This is expected to replace electronic devices because of its low risk of complications and the ability to respond to emotion. Here we survey the contemporary development of the bio-pacemaker by both experimental and computational approaches. The former mainly includes gene therapy and cell therapy, whilst the latter involves the use of multi-scale computer models of the heart, ranging from the single cell to the tissue slice. Up to now, a bio-pacemaker has been successfully applied in big mammals, but it still has a long way from clinical uses for the treatment of human heart diseases. It is hoped that the use of the computational model of a bio-pacemaker may accelerate this process. Finally, we propose potential research directions for generating a bio-pacemaker based on cardiac computational modeling.
概要
起搏功能障碍已成为威胁人类健康的一种重大疾病, 严重时可能导致心律失常、 晕厥, 甚至死亡. 到目前为止, 治疗起搏功能障碍的最佳方案是植入电子起搏器. 但是它存在一些缺点, 例如电池寿命有限, 手术过程具有感染的风险, 起搏频率单一等. 因此, 对生物起搏器的研究显得尤为迫切. 生物起搏器不但引起并发症的风险较低, 而且能够对生理情绪做出反应, 从而有望替代电子起搏器, 进行心脏起搏障碍治疗. 本文从生物实验和计算机模拟两方面对生物起搏器的发展进行综述. 前者主要包括基因疗法和细胞疗法的实验成果, 而后者介绍了多尺度的心脏建模从单个细胞到组织切片进行起搏器研究的进展. 迄今为止, 生物起搏器已被应用于大型哺乳动物实验, 但将其应用于临床心脏病治疗, 仍有很长的路要走. 利用计算机模型对生物起搏器诱发过程进行建模, 有望加速研究进程. 在本文中, 我们首先回顾了生物起搏器实验研究的发展, 然后介绍了生物起搏器计算机模型的目前的相关工作. 最后, 我们提出了基于心脏计算机模型研究生物起搏器的潜在研究方向.
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Yacong LI performed the literature research, wrote and edited the manuscript. Kuanquan WANG participated in the conceptualization, and reviewed and edited the manuscript. Qince LI investigated and collected the experiment data, and wrote the manuscript. Henggui ZHANG participated in the conceptualization, and writing and editing of the manuscript. All authors have read and approved the final manuscript.
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Yacong LI, Kuanquan WANG, Qince LI, and Henggui ZHANG declare that they have no conflict of interest.
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Project supported by the National Natural Science Foundation of China (Nos. 61572152, 61601143, and 81770328), the Science Technology and Innovation Commission of Shenzhen Municipality (Nos. JCYJ20151029173639477 and JSGG20160229125049615), and the China Postdoctoral Science Foundation (No. 2015M581448)
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Li, Y., Wang, K., Li, Q. et al. Biological pacemaker: from biological experiments to computational simulation. J. Zhejiang Univ. Sci. B 21, 524–536 (2020). https://doi.org/10.1631/jzus.B1900632
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DOI: https://doi.org/10.1631/jzus.B1900632