Electrophysiological Implications of Cardiac Bidomain

描述(由申请人提供)：Bidomain模型描述了心脏组织的三维、合体(电缆状)电特性，从而在与分子电生理学相关的亚微米空间尺度与心脏激活和纤颤的毫米和厘米尺度之间提供了生理上的现实联系。前五年的工作表明，各向异性双域可以解释用穴位刺激观察到的虚拟电极和磁场模式。这种具有纤维旋转和曲率的模型已经取代锯齿模型，成为描述心脏对除颤强度冲击反应的最有可能的竞争者。具有精确膜动力学的Bidomain模型几乎可以再现宏观心脏电活动中观察到的所有特征。研究的目标是继续使用Bidomain模型和一套先进的实验、分析和数值技术来探索心脏组织结构和心脏电活动之间的关系，特别是心脏磁场的产生和心脏对电刺激的反应。其具体目的是探索外加电击改变心肌组织宏观区域跨膜电位分布的机制；(2)发展测量和分析技术以确定关键双域参数的实际值；(3)测量离体心标本的心脏磁场，以探索跨膜电位、刺激电流和动作电流以及纤维构筑与电各向异性之间的关系；(4)探索折返、纤颤和除颤过程中心脏双域、相位奇异性和顺序刺激之间的关系；(5)研究阻尼性传播的动力学及其在折返性传播的形成和终止中的作用；(6)设计和应用先进的光学和磁学仪器来研究离体心组织的电活动；(7)探索相空间分析和图像处理的能力和局限性，以了解刺激、折返和除颤的动态行为；以及(8)继续发展和完善数值心脏双域模型。这项研究可能会导致更有效的心脏起搏器和除颤器，并改进对冠心病的磁心图诊断。

DESCRIPTION (provided by applicant): The bidomain model describes the three-dimensional, syncytial (cable-like) electrical properties of cardiac tissue, and thereby provides a physiologically realistic link between the sub-micron spatial scale associated with molecular electrophysiology and the millimeter and centimeter scales of cardiac activation and fibrillation. The preceding five years of work demonstrated that the anisotropic bidomain can explain the virtual electrode and magnetic field patterns observed with point stimulation. This model with fiber rotation and curvature has replaced the sawtooth model as the most likely contender for describing the response of the heart to defibrillation-strength shocks. The bidomain model with accurate membrane kinetics can reproduce almost all features observed in macroscopic cardiac electrical activity. The research objective is to continue using the bidomain model and a suite of advanced experimental, analytical, and numerical techniques to probe the relationship between cardiac tissue architecture and cardiac electrical activity, with a particular focus on the production of the cardiac magnetic field and the response of the heart to electrical stimulation. The specific aims are to explore the mechanisms by which externally applied shocks alter the transmembrane potential distribution over macroscopic regions of cardiac tissue; (2) develop measurement and analytical techniques to determine realistic values for the key bidomain parameters; (3) measure the cardiac magnetic field from isolated heart preparations to explore the relationships between the transmembrane potential, stimulus and action currents, and fiber architecture and electrical anisotropy; (4) explore the relation between the cardiac bi-domain, phase singularities, and sequential stimuli during reentry, fibrillation, and defibrillation; (5) study the dynamics of damped propagation and its role in formation and termination of reentrant propagation; (6) devise and apply advanced optical and magnetic instrumentation to study the electrical activity of isolated cardiac tissue; (7) explore the capabilities and limitations of phase space analysis and image processing to understand the dynamic behavior of stimulation, reentry and defibrillation; and (8) continue to develop and refine numerical cardiac bidomain models. This research may lead to more efficient cardiac pacemakers and defibrillators and improved magnetocardiographic diagnosis of coronary heart disease.