Electrophysiological Implications of Cardiac Bidomain

bidomain模型描述了心脏的三维，合胞体（电缆状）电特性。 组织，从而提供了亚微米空间尺度之间的生理现实的联系， 用分子电生理学和心脏激活的毫米和厘米尺度， 纤维性颤动前五年的工作表明，各向异性的生物质可以解释 虚拟电极和用点刺激观察的磁场模式。这个有纤维旋转的模型 和曲率已经取代了ESTA模型作为最有可能的竞争者描述的反应， 心脏除颤强度电击。具有精确的膜动力学的bidomain模型可以 再现了在宏观心脏电活动中观察到的几乎所有特征。研究目的是 继续使用bidomain模型和一套先进的实验，分析和数值模拟， 技术来探测心脏组织结构和心脏电活动之间的关系， 特别关注心脏磁场的产生和心脏对电流的响应， 刺激.具体的目的是探讨外部施加的冲击改变 心脏组织宏观区域的跨膜电位分布;（2）开发测量 和分析技术，以确定关键生物主要参数的实际值;（3）测量 从离体心脏制备的心脏磁场，以探讨 跨膜电位、刺激和动作电流、纤维结构和电各向异性;（4） 探索心脏双域，相位奇点和连续刺激之间的关系， 折返、纤颤和除颤;（5）研究阻尼传播的动力学及其在形成中的作用 设计并应用先进的光、磁技术， 仪器研究离体心脏组织的电活动;（7）探索的能力， 相空间分析和图像处理理解刺激的动态行为的局限性， （8）继续发展和完善心脏双脉肌的数值模型。这 研究可能会导致更有效的心脏起搏器和心脏起搏器， 冠心病的心磁图诊断。 PEI_PORMANCE ; 5 tTF（S）（组织、城市、州） 范德比尔特大学 纳什维尔，田纳西州37235 关键人员。请参见说明，根据需要使用续页以提供所需信息， 从主要研究者开始，按字母顺序列出所有其他关键人员，姓在前。 名称机构 约翰·维克斯沃范德比尔特大学 范德比尔特大学 作者：James C.杜兰大学 丹尼尔·戈蒂埃杜克大学 作者声明：Jonathan M.范德比尔特大学 作者：Jenny R.范德比尔特大学 米加范德比尔特大学 罗斯，布拉德利J.奥克兰大学 维尼亚明范德比尔特大学西多罗夫 Trayanova，娜塔莉亚A.杜兰大学 格式如下所示。 在项目中的作用 主要研究者 研究助理教授 副研究员 副教授 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。参见说明。[]是[]否 PHS 398（修订版，05/01）第2页__表格第2页o Prncpa nvestgator/Program Director（Last，First，Middle）：Wikswo，John Peter，Jr. 主要研究者/项目负责人的姓名必须在打印页和续页的顶部提供。 研究资助 目录 页码 首页...... 1 说明，

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,