二维心脏组织中尖端扭转型室性心动过速离子机制的模拟研究。

Simulation study of the ionic mechanisms underlying Torsade de Pointes in a 2D cardiac tissue.

机构信息

Biomedical Engineering Group, Department of Applied Mechanics, Indian Institute of Technology Madras, Chennai 600036, India.

出版信息

Comput Biol Med. 2017 Oct 1;89:293-303. doi: 10.1016/j.compbiomed.2017.08.017. Epub 2017 Aug 24.

DOI:10.1016/j.compbiomed.2017.08.017

PMID:28858645

Abstract

BACKGROUND

To understand the ionic mechanism behind the genesis of Torsade de Pointes (TdP) occurring with long QT syndrome 2 (LQTS2) in a remodelled transmural tissue.

METHODS

The TP06 model is used to simulate the electrical activity of cells in a 2D transmural ventricular model. LQTS2 is realised by reducing the potassium current (I) to 0.5 in each cell. Each cell of the tissue is remodelled by increasing the conductance of calcium current (G). The above two factors make the cells prone to early after depolarizations (EADs) development. The rise in G that can develop a sustained TdP at normal pacing rate is determined from this study. A look at the calcium dynamics, sodium-calcium exchanger current (I) and slow delayed rectifier potassium current (I) distribution maps of the tissue helps us in analysing the mechanism of TdP generation.

RESULTS

A TdP type pattern at normal pacing rate is generated when G is more than 3.5 times the control parameter. From the M-cell island, an adequate number of cells spontaneously release calcium from their sarcoplasmic reticulum leading to increased intracellular calcium and inward sodium current through the sodium calcium exchanger current (I). These contribute to the development of EADs which create a depolarising wavefront that triggers TdP in the tissue. When G is less than 3.5 times the control value, premature ventricular complexes (PVC) occur interspersed between normal beats.

CONCLUSION

Normal pacing rates can induce a multi focal TdP when sufficient number of M-cells simultaneously undergo spontaneous calcium release (SCR) events.

摘要

背景

为了了解长 QT 综合征 2（LQTS2）在重构的透壁组织中发生尖端扭转型室性心动过速（TdP）的离子机制。

方法

使用 TP06 模型模拟 2D 透壁心室模型中细胞的电活动。通过将每个细胞的钾电流（I）降低到 0.5 来实现 LQTS2。通过增加钙电流（G）的电导来重构组织中的每个细胞。这两个因素使细胞容易发生早期后除极（EADs）的发展。从这项研究中确定了可以在正常起搏率下发展持续 TdP 的 G 的上升。观察组织的钙动力学、钠钙交换电流（I）和慢延迟整流钾电流（I）分布图有助于我们分析 TdP 产生的机制。

结果

当 G 大于控制参数的 3.5 倍时，在正常起搏率下会产生 TdP 类型的模式。从 M 细胞岛，足够数量的细胞从其肌浆网中自发释放钙，导致细胞内钙增加和通过钠钙交换电流（I）的内向钠电流。这些有助于 EADs 的发展，从而产生引发组织中 TdP 的去极化波前。当 G 小于控制值的 3.5 倍时，正常搏动之间会出现室性早搏（PVC）。