MECHANOELECTRICAL FEEDBACK IN HEART: ARRHYTHMIAS

心脏的机电反馈：心律失常

• 批准号: 6122487
• 负责人: WILLIAM CRAELIUS
• 金额: --
• 依托单位: MELLON PITTS CORPORATION (MPC CORP)
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6122487
• 关键词: Mammalia; bioengineering /biomedical engineering; biomedical resource; cardiovascular system; model design /development

An electrical network model of ventricular heart tissue was constructed from > 10,000 model cardiac myocytes. Each modeled myocyte is assembled from > 100 patches of membrane elements, consisting of membrane capacitance, represented by equivalent capacitor, membrane resistance, represented by equivalent resistor, voltage-gate sodium, potassium, calcium channels, and stretch-activated channels. Nonlinear electrical components modeling the dynamic behavior of ion channels in each membrane element were designed based on nonlinear differential equations and the experiment data of patch clamp on single cardiac myocyte. Membrane elements was connected longitudinally by passive resistive elements, and each modeled cell was connected laterally to adjacent modeled cell through a gap junction, represent by a resistor, forming a two dimensional modeled ventricular tissue. This approach shows that SPICE, a circuit simulator, on a supercomputer could provide the speed and accuracy necessary to accomplish the goal of this study. Our previous lab work on modeling single myocyte simulated on SPICE (PC version) demonstrated that the triggering of action current could be activated directly by current from stretch-activated channels, and blocking potassium channel both positively and negatively influences stretch-induced arrhythmias (SIAs). In this study, a bi-domain electrical network model of ventricular tissue, consisting of over hundred thousands of elements, combined with ion channels data can provide simulated view not only on cell level but also macrostructure level. A particular stimulus protocol was designed in this study to investigate the interaction between timing of ventricular stretch and other membrane currents, in determining conduction velocity, charge threshold, and action potential duration. The goal of the research is to find new strategies for treating arrhythmais.

建立了心肌组织的电网络模型。 由10,000个模型心肌细胞构建而成。每个都已建模 肌细胞由100块膜元件组装而成， 由膜电容组成，用当量表示 电容器，膜电阻，用等效电阻表示， 电压门控钠、钾、钙通道和 拉伸激活的通道。非线性电气元件建模 每个膜元件中离子通道的动态行为是 基于非线性微分方程组的设计与实验 单个心肌细胞膜片钳数据。膜元件是 由无源电阻元件纵向连接，每个 建模单元通过横向连接到相邻的建模单元 一种由电阻表示的缝隙结，形成二维的 模拟的脑室组织。这种方法表明，SPICE，一种电路 仿真器，在超级计算机上可以提供速度和精度 完成本研究的目标所必需的。我们以前的实验室工作 基于SPICE(PC版)的单个心肌细胞建模 演示了动作电流的触发可以被激活 直接通过拉伸激活通道的电流，并阻断 钾通道既有积极的影响，也有消极的影响 牵张性心律失常(SIAS)。在这项研究中，一个双域 心室组织的电网络模型，由Over 数十万种元素，结合离子通道数据可以 不仅提供单元级别的模拟视图，还提供宏观结构的模拟视图 水平。在这项研究中设计了一种特殊的刺激方案来 探讨室壁牵张时间与心功能之间的相互作用 其他膜电流，在确定传导速度时，电荷 阈值和动作电位时程。这项研究的目标是 寻找治疗心律失常的新策略。