Okada Jun-Ichi, Washio Takumi, Sugiura Seiryo, Hisada Toshiaki
UT-Heart Inc., Tokyo 154-0003, Japan.
Future Center Initiative, The University of Tokyo, Chiba 277-0871, Japan.
Korean J Physiol Pharmacol. 2019 Sep;23(5):295-303. doi: 10.4196/kjpp.2019.23.5.295. Epub 2019 Aug 26.
A heart simulator, UT-Heart, is a finite element model of the human heart that can reproduce all the fundamental activities of the working heart, including propagation of excitation, contraction, and relaxation and generation of blood pressure and blood flow, based on the molecular aspects of the cardiac electrophysiology and excitation-contraction coupling. In this paper, we present a brief review of the practical use of UT-Heart. As an example, we focus on its application for predicting the effect of cardiac resynchronization therapy (CRT) and evaluating the proarrhythmic risk of drugs. Patient-specific, multiscale heart simulation successfully predicted the response to CRT by reproducing the complex pathophysiology of the heart. A proarrhythmic risk assessment system combining channel assays and simulation of cardiac electrophysiology using UT-Heart successfully predicted druginduced arrhythmogenic risk. The assessment system was found to be reliable and efficient. We also developed a comprehensive hazard map on the various combinations of ion channel inhibitors. This electrocardiogram database (now freely available at http://ut-heart.com/) can facilitate proarrhythmic risk assessment without the need to perform computationally expensive heart simulation. Based on these results, we conclude that the heart simulator, UT-Heart, could be a useful tool in clinical medicine and drug discovery.
心脏模拟器UT-Heart是一个人体心脏的有限元模型,它能够基于心脏电生理学和兴奋-收缩偶联的分子层面,再现工作心脏的所有基本活动,包括兴奋的传播、收缩、舒张以及血压和血流的产生。在本文中,我们简要回顾了UT-Heart的实际应用。例如,我们重点介绍了其在预测心脏再同步治疗(CRT)效果和评估药物致心律失常风险方面的应用。通过再现心脏复杂的病理生理学,针对特定患者的多尺度心脏模拟成功预测了对CRT的反应。一个结合通道分析和使用UT-Heart进行心脏电生理模拟的致心律失常风险评估系统成功预测了药物诱发的心律失常风险。该评估系统被发现是可靠且高效的。我们还针对离子通道抑制剂的各种组合绘制了一张综合风险图。这个心电图数据库(现在可在http://ut-heart.com/免费获取)无需进行计算成本高昂的心脏模拟就能促进致心律失常风险评估。基于这些结果,我们得出结论,心脏模拟器UT-Heart可能是临床医学和药物研发中的一个有用工具。