Electrophysiological Implications of Cardiac Bidomain

Bidomain模型描述了心脏的三维、合胞(电缆状)电特性 组织，从而在相关的亚微米空间尺度之间提供了生理上真实的联系 分子电生理学和毫米级和厘米级的心脏激活和 纤颤。前五年的工作表明，各向异性的双多体可以解释 用穴位刺激观察虚拟电极和磁场模式。这种带光纤旋转的模型 曲率模型已经取代锯齿模型，成为最有可能描述 心脏要除颤--力量震荡。具有精确膜动力学的Bidomain模型可以 重现了在宏观心脏电活动中观察到的几乎所有特征。研究的目标是 继续使用Bidomain模型和一套高级实验、分析和数值计算 探索心脏组织结构和心脏电活动之间的关系的技术， 特别关注心脏磁场的产生和心脏对电的反应 刺激。其具体目标是探索外部冲击通过何种机制改变 心肌组织宏观区域跨膜电位分布；(2)发展测量 和分析技术来确定关键双域参数的真实值；(3)测量 从心脏磁场离体心制剂中探讨二者之间的关系 跨膜电位、刺激和动作电流、纤维结构和电各向异性；(4) 探讨心脏双域、位相奇异性和序列刺激之间的关系 再入、纤颤和除颤；(5)研究衰减传播的动力学及其在编队中的作用 和折返传播的终止；(6)设计和应用先进的光学和磁学 研究离体心组织电活动的仪器；(7)探索能力和 相空间分析和图像处理在理解刺激的动态行为方面的局限性， 再入和除颤；以及(8)继续发展和完善数字心脏双项模型。这 研究可能导致更有效的心脏起搏器和除颤器，并改进 心磁图对冠心病的诊断。 PEI_PORMANCE；5tTF(S)(组织、市、州) 范德比尔特大学 田纳西州纳什维尔，邮编：37235 关键人员。请参阅说明，根据需要使用续页在中提供所需信息 从首席调查员开始，按字母顺序列出所有其他关键人员，姓氏在前。 名称：组织 约翰·P·维克斯沃范德比尔特大学 鲍登巴赫，弗朗茨·J·范德比尔特大学 詹姆士·C·杜兰大学伊森 丹尼尔·J·杜克大学高蒂尔 乔纳森·M·范德比尔特大学吉利根 珍妮·R·范德比尔特大学霍尔泽 迈克尔·I·范德比尔特大学 布拉德利·J·奥克兰大学 西多罗夫，维尼亚明·范德比尔特大学 特拉亚诺娃，纳塔莉亚·A·杜兰大学 格式如下所示。 在项目中的角色 首席调查员 助理研究助理教授 副研究员 副教授 助理研究助理教授 研究助理 助理教授 副教授 研究助理 副教授 披露许可声明。仅适用于SBIR/STTR。请参阅说明。[]是[]否 小灵通398(版本，05/01)第2页__表第2页o Prncpa nvestgator/计划总监(最后、第一、中间)：Wikswo，John Peter，Jr. 必须在每张打印页和每张续页的顶部提供首席调查员/项目主任的姓名。 研究补助金 目录 页码 主页........................................................................................................................1 描述，

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. PEI_PORMANCE ;5tTF(S) (organization, city, state) Vanderbilt University Nashville, TN 37235 KEY PERSONNEL. See instructions, Use continuation pages as needed to provide the required information in Start with Principal Investigator, List all other key personnel in alphabetical order, last name first. Name Organization John P. Wikswo Vanderbilt University Baudenbacher, Franz J. Vanderbilt University Eason, James C. Tulane University Gauthier, Daniel J. Duke University Gilligan, Jonathan M. Vanderbilt University Holzer, Jenny R. Vanderbilt University Miga, Michael I. Vanderbilt University Roth, Bradley J. Oakland University Sidorov, Veniamin Vanderbilt University Trayanova, Natalia A. Tulane University the format shown below. Role on Project Principal Investigator Research Asst. Professor Associate Research Fellow Associate Professor Research Asst. Professor Research Associate Assistant Professor Associate Professor Research Associate Associate Professor Disclosure Permission Statement. Applicable to SBIR/STTR Only. See instructions. [] Yes [] No PHS 398 (Rev, 05/01) Page 2__ Form Page 2 o Prncpa nvestgator/Program Director (Last, first, middle): Wikswo, John Peter, Jr. The name of the principal investigator/program director must be provided at the top of each printed page and each continuation page. RESEARCH GRANT TABLE OF CONTENTS Page Numbers Face Page .................................................................................................................................................. 1 Description,