ELECTROPHYSIOLOGICAL IMPLICATIONS OF CARDIAC BIDOMAIN

描述（改编自申请人的摘要）： 电活动通过心室心肌的传播需要 了解单个心脏细胞的电行为，以及 心脏合胞体的作用。 该项目将利用电力， 离体兔心脏激动的磁、光标测 心脏和用bidomain模型连接离子通道的数值模拟 从动力学到宏观电学行为。 在bidomain模型中，心脏 组织是具有各向异性的三维（3-D）电缆， 由非线性细胞分隔的细胞内外空间 膜的 最近的实验证实了这个模型的有效性， 不相等的细胞内和细胞外各向异性，并证明了重要的 虚拟阴极和阳极在心脏对电刺激的反应中的作用 刺激. 这项提案的目的是探索不良 心脏电生理学中的已知现象可能是 不平等的各向异性，并将由此产生的知识应用于问题， 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）复极化的扩展，以及（3） 对外界电刺激的反应。 这将需要（4）细化 先进的电子、光学和磁记录技术， 研究人员已经开发的数值方法，并可能需要 (5)bidomain模型的扩展以包括组织异质性。 有待检验的假设包括：灌注浴降低了上升率 心尖部的螺旋纤维几何形状 产生无电磁场; MCG T波在 心率高，而MCG QRS、ECG QRS和ECT T波则不高; 不相等的双肌各向异性和组织界面决定了 损伤电流场.阳极和阴极强度-间隔曲线 包含接通和断开部分;阳极强度间隔中的倾角 曲线对应于阳极中断刺激;虚拟电极是 在双极和双相刺激中都很重要; SQUID磁力计 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 所需的电子和光学仪器已经 开发;扫描高分辨率SQUID磁强计阵列将 构建用于标测离体兔心外膜磁场的 心 这项研究可以阐明电各向异性在 传播和复极化，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.