Reilly Louise, Josvai Mitchell, Kalluri Manasa, Anderson Corey L, Ni Haibo, Orland Kate M, Lang Di, Glukhov Alexey V, Grandi Eleonora, Eckhardt Lee L
Cellular and Molecular Arrhythmia Research Program, Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Department of Pharmacology, University of California-Davis, Davis, California, USA.
JACC Clin Electrophysiol. 2024 Dec;10(12):2628-2632. doi: 10.1016/j.jacep.2024.07.014. Epub 2024 Sep 18.
Idiopathic ventricular fibrillation (IVF) is an unrefined diagnosis representing a heterogeneous patient group without a structural or genetic definition. IVF treatment is not mechanistic-based due to the lack of experimental patient-models. We sought to create a methodology to assess cellular arrhythmia mechanisms for IVF as a proof-of-concept study. Using IVF patient-specific induced pluripotent stem cell-derived cardiomyocytes, we integrate electrophysiological optical mapping with computational modeling to characterize the cellular phenotype. This approach flips the traditional paradigm using a biophysically detailed computational model to solve the problem inversely. Insight into the cellular mechanisms of this patient's IVF phenotype could also serve as a therapeutic testbed.
特发性室颤（IVF）是一种未经细化的诊断，代表了一组无结构或基因定义的异质性患者群体。由于缺乏实验性患者模型，IVF的治疗并非基于机制。我们试图创建一种方法来评估IVF的细胞心律失常机制，作为一项概念验证研究。利用IVF患者特异性诱导多能干细胞衍生的心肌细胞，我们将电生理光学映射与计算建模相结合，以表征细胞表型。这种方法颠覆了传统范式，使用生物物理细节丰富的计算模型来反向解决问题。对该患者IVF表型的细胞机制的深入了解也可作为一个治疗试验台。
