MECHANOELECTRICAL FEEDBACK IN HEART: ARRHYTHMIAS

心脏的机电反馈：心律失常

• 批准号: 6282522
• 负责人: WILLIAM CRAELIUS
• 金额: $ 1.19万
• 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/6282522
• 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.

建立了心室组织电网络模型， 由> 10，000个模型心肌细胞构建。 每个建模 肌细胞由> 100片膜元件组装而成， 由膜电容组成，用等效电容表示 电容器，膜电阻，用等效电阻表示， 电压门控钠、钾、钙通道， 牵张激活的通道 非线性电气元件建模 在每个膜元件中离子通道的动力学行为是 基于非线性微分方程和实验设计 单个心肌细胞膜片钳数据。 膜元件是 通过无源电阻元件纵向连接，并且每个 模型化单元通过以下方式横向连接到相邻的模型化单元 间隙结，由电阻器表示，形成二维 模拟心室组织。 这种方法表明，SPICE，一个电路， 超级计算机上的模拟器可以提供速度和准确性 这是实现本研究目标所必需的。 我们之前的实验室工作 在SPICE（PC版）上模拟单个心肌细胞 证明了动作电流的触发可以被激活 直接通过来自牵张激活通道的电流， 钾离子通道既有积极影响，也有消极影响 牵张性心律失常（SIAs）。 在这项研究中， 心室组织的电网络模型，包括 数十万种元素，结合离子通道数据， 不仅提供单元级的模拟视图，而且提供宏观结构的模拟视图 水平 本研究设计了一种特殊的刺激方案， 研究心室牵张时间和 其他膜电流，在确定传导速度，电荷 阈值和动作电位时程。 研究的目的是 来寻找治疗疟疾的新策略