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.

心脏心脏组织的电网络模型是 由> 10,000个型号心肌细胞构建。 每个建模 肌细胞是从> 100个膜元素斑块组装的， 由膜电容组成，以等效为代表 电容器，膜电阻，以等效电阻为代表 电压果钠，钾，钙通道和 拉伸激活的通道。 非线性电气组件建模 每个膜元素中离子通道的动态行为是 基于非线性微分方程和实验设计 单个心肌细胞上斑块夹的数据。 膜元素是 通过被动电阻元件纵向连接，每个元件 模型的单元通过横向连接到通过 由电阻表示的间隙连接点，形成二维 模型的心室组织。 这种方法表明Spice是电路 模拟器，在超级计算机上可以提供速度和准确性 实现这项研究的目标所必需的。 我们以前的实验室工作 建模在香料（PC版本）上模拟的单个心肌细胞 证明可以激活动作电流的触发 直接通过拉伸激活通道的电流，并阻止 钾通道既积极和负面影响 拉伸诱导的心律不齐（SIA）。 在这项研究中，双域 心室组织的电网络模型，由过度组成 数十万个元素与离子通道数据相结合可以 不仅提供模拟视图，而且还提供宏观结构 等级。 在本研究中设计了特定的刺激方案 研究心室伸展时间和 在确定传导速度时，其他膜电流充电 阈值和动作潜在持续时间。 研究的目的是 寻找治疗心脏不良的新策略。