ELECTROPHYSIOLOGICAL IMPLICATIONS OF CARDIAC BIDOMAIN

描述(改编自申请者摘要)：对 通过心室肌传播电活动需要 了解单个心肌细胞的电学行为，以及 心脏合胞体的作用。该项目将利用电力， 离体兔心脏活动的磁学和光学标测 连接离子通道的Bidomain模型的心脏和数值模拟 宏观电学行为的动力学。在Bidomain模型中，心脏 组织是具有各向异性的三维(3-D)电缆 由一个非线性细胞分隔的细胞内和细胞外空间 薄膜。最近的实验证实了该模型的有效性 不相等的细胞内和细胞外各向异性，并证明了重要的 虚拟阴阳极在心脏电反应中的作用 刺激。这项提议的目的是探索糟糕的 了解心脏电生理学的现象，可能是 不相等的各向异性，并将所得到的知识应用于 心脏刺激和除颤。具体目标是确定 电各向异性和组织宏观结构如何影响(1) 去极化的传播(2)复极化的传播，以及(3) 对外界电刺激的反应。这将需要改进。 先进的电、光和磁记录技术以及 调查人员已经开发的数值方法，可能需要 (5)将Bidomain模型扩展到包括组织异质性。 有待检验的假设包括：洗澡可以降低上升的速度。 关于动作电位；心尖部的螺旋纤维几何形状 产生无声电磁场；MCG T波在 心率高，而心电QRS、心电图QRS和ECT T波不高； 不相等的双峰各向异性和组织界面决定了大小 损伤电流产生的电场.阳极和阴极强度-间隔曲线 包含成败部分；阳极强度区间的倾角 曲线对应于阳极断点刺激；虚拟电极 在双极和双相刺激中都很重要；SQUID磁强计 阵列可以成像除颤电流和心脏纤维曲率 强烈影响跨膜电位分布 除颤。所需的电气和光学仪器已经 开发了扫描高分辨率SQUID磁强计阵列 构建用于标测离体兔心外膜磁场的方法 心。这项研究可以阐明电各向异性在 传播和复极，以及在刺激和除颤期间 心脏。

DESCRIPTION (Adapted from Applicant's Abstract): An understanding of the propagation of electrical activity through ventricular myocardium requires knowledge of both the electrical behavior of an individual cardiac cell, and the role of the cardiac syncytium. This project will utilize electric, magnetic, and optical mapping of cardiac activation in the isolated rabbit heart and numerical simulations with the bidomain model to link ion channel kinetics to macroscopic electrical behavior. In the bidomain model, cardiac tissue is a three dimensional (3-D) electrical cable with anisotropic intra-and extracellular spaces that are separated by a nonlinear cell membrane. Recent experiments confirm the validity of this model with unequal intra- and extracellular anisotropies, and demonstrate the important role of virtual cathodes and anodes in the cardiac response to electrical stimulation. The objectives of this proposal are to explore poorly understood phenomena in cardiac electrophysiology that may be the result of unequal anisotropies, and to apply the resulting knowledge to problems in cardiac stimulation and defibrillation. The Specific Aims are to determine how electrical anisotropies and tissue macrostructure affect (1) the propagation of depolarization (2) the spread of repolarization, and (3) the response to external electrical stimuli. This will require (4) refinement of the advanced electrical, optical, and magnetic recording techniques and numerical methods already developed by the investigators, and may require (5) extension of the bidomain model to include tissue heterogeneities. Hypotheses to be tested include: a perfusing bath reduces the rate of rise of the action potential; the spiral fiber geometry at the cardiac apex produces electrically-silent magnetic fields; the MCG T-wave is altered at high heart rates whereas the MCG QRS, ECG QRS, and ECT T-wave are not; unequal bidomain anisotropies and tissue interfaces determine the magnitude fields from injury currents; anodal and cathodal strength-interval curves contain make and break sections; the dip in the anodal strength-interval curve corresponds to anodal-break stimulation; virtual electrodes are important in both bipolar and biphasic stimulation; a SQUID magnetometer array can image defibrillation currents; and cardiac fiber curvature strongly affects the transmembrane potential distribution during defibrillation. The required electrical and optical instruments are already developed; a scanning high resolution SQUID magnetometer array will be constructed for mapping the epicardial magnetic field of the isolated rabbit heart. This research could clarify the role of electrical anisotropy during propagation and repolarization, and during stimulation and defibrillation of the heart.