NUMERICAL SIMULATION OF CARDIAC ELECTROPHYSIOLOGY

描述(改编自申请人的摘要)：的主要目标 这项建议是为了更好地理解电刺激。1)第一个 具体目的是计算强度-层间曲线。这个 强度-时间间隔曲线在确定应力分布中起着重要作用。 心脏组织的兴奋性。初步研究表明，这个形状 强度-间隔曲线的大小由复杂的相互作用决定 在空间上不均匀的跨膜电位分布和 膜离子通道的非线性特性。一个假设是 更复杂的心脏组织模型也会导致类似的形状 强度-间隔曲线。实验表明，强度-时间间隔曲线 电极植入心脏后会随时间变化。一个 假说是电极周围的组织损伤导致了阳极 强度-间隔曲线随时间移动到更大的间隔。2) 第二个具体目的是阐明再入诱导的机制。 初步研究预测，组织耐火材料的一种改良 跨膜电位分布不均匀引起的周期 在刺激电极周围会引起再入，但再入波 前线不稳。一个假设是心脏组织的一个更好的模型 将预示着一种稳定的、可再入的模式。3)第三个具体目标是 确定电穿孔将如何影响刺激阈值和 重返大气层。在单极电极的电刺激过程中， 跨膜电位可以达到发生电穿孔的水平。一个 假说是电穿孔会将阴极阈值改变为 大于阳极阈值的范围。4)第四个具体目标是 计算两相刺激的强度-时间间隔曲线。一个 假说是双相刺激会影响“中断”刺激到 比“制造”刺激更大的程度。5)第五个具体目标是 确定非均质性对心脏单极刺激的影响 组织。基于比多曼模型的计算机模拟将被用于 实现这些具体目标，并检验这些假设。

DESCRIPTION (adapted from the applicant's abstract): The primary goal of this proposal is to better understand electrical stimulation. 1) The first specific aim is to calculate the strength-interval curve. The strength-interval curve plays an important role in determining the excitability of cardiac tissue. Preliminary studies suggest that the shape of the strength-interval curve is determined by a complex interaction between the spatially inhomogeneous transmembrane potential distribution and the nonlinear properties of the membrane ionic channels. A hypothesis is that more sophisticated models of cardiac tissue also lead to similar shaped strength-interval curves. Experiments show that the strength-interval curve changes with time after an electrode is implanted in the heart. A hypothesis is that tissue damage around the electrode causes the anodal strength-interval curve to shift to larger intervals with time. 2) The second specific aim is to clarify the mechanism of reentry induction. Preliminary studies predict that a modification of the tissue refractory period arising from the inhomogeneous transmembrane potential distribution around a stimulating electrode causes reentry, but that the reentrant wave front is not stable. A hypothesis is that a better model of cardiac tissue will predict a stable, reentrant pattern. 3) The third specific aim is to determine how electroporation will affect stimulation thresholds and reentry. During electrical stimulation from a unipolar electrode, the transmembrane potential can reach levels at which electroporation occurs. A hypothesis is that electroporation will change the cathodal threshold to a greater extent than the anodal threshold. 4) The fourth specific aim is to calculate the strength-interval curves for biphasic stimulation. A hypothesis is that biphasic stimulation will affect "break" stimulation to a greater extent than "make" stimulation. 5) The fifth specific aim is to determine the effect of inhomogeneities on unipolar stimulation of cardiac tissue. Computer simulations based on the bidomain model will be used to achieve these specific aims and test these hypotheses.