Mechanistic Insights Into Inflammation-Induced Arrhythmias: A Simulation Study.
Mechanistic Insights Into Inflammation-Induced Arrhythmias: A Simulation Study.
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DOI：
10.3389/fphys.2022.843292
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发表时间：
2022
影响因子：
4
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中科院分区：
文献类型：
--
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心血管疾病是人类死亡的主要原因，其中，室性心律失常是最常见的死亡原因。有合理的证据表明炎症是室颤（VF）的病因。在由过度活跃的免疫反应引起的全身性炎症的情况下，诱导的炎性细胞因子直接影响心肌细胞中离子通道的功能，导致动作电位时程（APD）延长。然而，炎症性尼古丁诱导的分子和细胞影响与炎症相关的室性心律失常之间的机制联系需要阐明。本研究旨在通过多尺度虚拟心脏模型确定全身炎症对心室电生理的潜在影响。关于三种主要细胞因子的离子电流的实验数据[即，将肿瘤坏死因子-α（TNF-α）、白细胞介素-1（IL-1β）和白细胞介素-6（IL-6）]掺入细胞模型中，并评价每种细胞因子及其联合作用对细胞动作电位（AP）的影响。此外，还在组织模型中研究了这些细胞因子对激发波传导的整体效应。结果表明，炎性细胞因子可显著延长动作电位时程，增强跨壁和局部复极不均一性，降低心室组织对快速心率的适应性。此外，模拟伪ECG显示QT间期延长-与临床观察结果一致的表现。总之，本研究为炎症相关的室性心律失常提供了新的见解。
Cardiovascular diseases are the primary cause of death of humans, and among these, ventricular arrhythmias are the most common cause of death. There is plausible evidence implicating inflammation in the etiology of ventricular fibrillation (VF). In the case of systemic inflammation caused by an overactive immune response, the induced inflammatory cytokines directly affect the function of ion channels in cardiomyocytes, leading to a prolonged action potential duration (APD). However, the mechanistic links between inflammatory cytokine-induced molecular and cellular influences and inflammation-associated ventricular arrhythmias need to be elucidated. The present study aimed to determine the potential impact of systemic inflammation on ventricular electrophysiology by means of multiscale virtual heart models. The experimental data on the ionic current of three major cytokines [i.e., tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1β), and interleukin-6 (IL-6)] were incorporated into the cell model, and the effects of each cytokine and their combined effect on the cell action potential (AP) were evaluated. Moreover, the integral effect of these cytokines on the conduction of excitation waves was also investigated in a tissue model. The simulation results suggested that inflammatory cytokines significantly prolonged APD, enhanced the transmural and regional repolarization heterogeneities that predispose to arrhythmias, and reduced the adaptability of ventricular tissue to fast heart rates. In addition, simulated pseudo-ECGs showed a prolonged QT interval—a manifestation consistent with clinical observations. In summary, the present study provides new insights into ventricular arrhythmias associated with inflammation.
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