MATHEMATICAL MODELS OF PROPAGATION IN CARDIAC CELLS

心脏细胞传播的数学模型

• 批准号: 3780670
• 负责人: DONALD C MICHAELS
• 金额: --
• 依托单位: UPSTATE MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3780670
• 关键词: action potentials; atrioventricular node; bioperiodicity; cellular pathology; computer simulation; electrophysiology; gap junctions; heart Purkinje's fiber; heart block; heart cell; heart conduction system; heart rate; heart ventricle; mathematical model; model design /development; myocardium; stimulus interval

Mathematical modelling, a supercomputer and massively parallel computer technology will be used to investigate basic electrophysiological processes involved in the initiation and propagation of the mammalian cardiac impulse, both under normal conditions and during disease states. Models of single atrioventricular (AV) nodal, Purkinje and ventricular cells will be used to perform numerical simulations for the study of complex non-linear dynamics and chaotic behavior. In single cell models, we will test the hypothesis that periodic rate-dependent activations patterns in single cardiac cells are a consequence of a non-linear recovery of excitability during diastole, and will develop an analytical model of excitability based on the recovery kinetics and voltage-dependence of the appropriate transmembrane currents, in an attempt to predict the precise dynamics of rate-dependent activation of single cardiac cells. We will also investigate the non-linear dynamics of propagation in one and two- dimensionally connected bundles of AV nodal cells, linear Purkinje fibers and branching Purkinje networks. We will study the influence of varying the regenerative properties of the individual elements, or the degree of electrical interaction among them. Localized zones of depressed conduction separating regions of normal activity will also be created by high resistance coupling and/or by low excitability, to test the hypothesis that rate-dependent conduction block is a result of the discontinuities in cell excitability, geometrical arrangements of cell-to-cell connections and/or electrical coupling. We will also analyze the response of these models to repetitive stimulation on the basis of the theory of dynamical systems (chaos theory), with particular attention paid to amplification or reduction of local beat-to-beat changes in activation parameters (e.g., latency, action potential duration, etc.) by propagation. The nature of propagation in isotropic and anisotropic ventricular muscle will be studied in models of one-and two-dimensional arrays of ventricular cells coupled through gap junctions. The interplay between intercellular coupling resistance an membrane generator properties, and their effects on conduction velocity and patterns of propagation will be investigated systematically. Further, we will determine whether functional block and circuitous pathways can be generated in these two-dimensional models as a consequence of the nonuniform anisotropic distribution of axial resistivity, and whether reentry requires a critical relationship between relative size and orientation of the region of block and the curvature of the wavefront reaching that region. Predictions from the simulations will be compared with experimental results obtained in other projects and model predictions will be used to design further biological experiments. Overall, the simulations will be used to probes the underlying cellular mechanisms of normal and abnormal heart rate and rhythm.

数学建模、超级计算机和大规模并行计算机 技术将用于研究基本的电生理过程 参与哺乳动物心脏的启动和繁殖 冲动，无论是在正常条件下，在疾病状态。 模型 单个房室（AV）结、浦肯野细胞和心室细胞将被 用于进行复杂非线性研究的数值模拟 动力学和混沌行为。 在单细胞模型中，我们将测试 假设周期性频率依赖性激活模式在单个 心肌细胞是兴奋性非线性恢复的结果 并将开发一个基于兴奋性的分析模型， 恢复动力学和电压依赖性的适当的 跨膜电流，试图预测的精确动态 单个心脏细胞的速率依赖性激活。 我们还将 研究传播的非线性动力学在一个和两个- 房室结细胞、线性浦肯野纤维的三维连接束 和分支浦肯野网络。 我们将研究不同的 单个元素的再生特性，或 它们之间的电相互作用。 传导抑制的局部区域 正常活动的分隔区域也将由高 电阻耦合和/或低兴奋性，以检验假设， 频率依赖性传导阻滞是细胞内不连续性的结果， 兴奋性、细胞间连接的几何排列和/或 电耦合 我们还将分析这些模型的响应， 基于动力系统理论的重复激励 （混沌理论），特别注意放大或 减少激活参数的局部逐搏变化（例如， 潜伏期、动作电位持续时间等）通过传播。 的性质 将研究各向同性和各向异性心室肌中的传播 在心室细胞的一维和二维阵列的模型中， 通过缝隙连接。 细胞间偶联 电阻膜发生器的性能，以及它们对 将研究传导速度和传播模式 系统地 此外，我们将确定功能块和 在这些二维模型中可以生成迂回路径， 轴向非均匀各向异性分布的结果 电阻率，以及再入是否需要一个关键的关系， 块体区域的相对大小和方向以及 波阵面到达该区域。 模拟预测将 与其他工程和模型的试验结果进行了比较 预测将用于设计进一步的生物实验。 总的来说，模拟将用于探测底层的细胞 正常和异常心率和节律的机制。