NONLINEAR DYNAMICS OF PROPAGATION IN ISOLATED HEART TISSUE

离体心脏组织中传播的非线性动力学

• 批准号: 6241980
• 负责人: Jose S Jalife
• 金额: $ 20.78万
• 依托单位: UPSTATE MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-01 至 1998-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6241980
• 关键词: action potentials; cell cell interaction; computer simulation; disease /disorder model; electrocardiography; electrophysiology; epicardial mapping; heart electrical activity; image processing; isolation perfusion; laboratory rabbit; magnetic resonance imaging; mathematical model; neural transmission; premature ventricular contractions; tachycardia; temperature; vector cardiography; ventricular fibrillation

Ventricular tachycardia (VT) and ventricular fibrillation (VF) may result from vortex-like reentrant excitation of the myocardium. Our general hypothesis is that, in the structurally normal heart, these arrhythmias are the result of 3-dimensional (3-D) electrical scroll waves activating the heart muscle at very high frequencies. To test this hypothesis, we will combine the use of high-resolution optical mapping, electrocardiography and vectorcardiography, together with mathematical modelling of the isolated rabbit hart. Our studies will be directed toward determining whether sustained monomorphic reentrant VT is the result of a stationary (anchored) scroll wave; whether polymorphic VT is the result of a nonstationary scroll wave; and whether VF is the result of the coexistence of a small n umber of nonstationary scroll waves. To this aim we will first characterize the electrical activity of the Langendorff-perfused heart in response to changes in specific parameters, such as temperature, action potential duration (APD), conduction velocity (CV) and basic cycle length, which may determine our ability to initiate vortex-like reentrant excitation. We will then study the role of spatial nonuniformities (i.e., gradients) in APD and CV in the genesis and subsequent evolution of vortex-like reentry, as well as in determining the type of arrhythmias (e.g., monomorphic or polymorphic VT; VF) that may occur. in addition, we will quantify the dynamics of spiral waves on the entire epicardial surface of the ventricles to establish whether such dynamics are consistent with 3-D scroll waves in excitable media. Further, we will use analytical tools to study the degree of spatial and temporal organization of wave propagation on the epicardial surface during t=sinus rhythm, ventricular pacing, VT and VF. To investigate three-dimensional aspects of wave propagation in these studies we will record three orthogonal ECG leads for the construction of 3-D vectorcardiographic loops while simultaneously obtaining optical maps of the entire ventricular surface. Finally, we will use a 3-D "cube" model, as well as a model of the intact right and left ventricles of the heart based on FitzHugh-Nagumo kinetics, and on realistic Magnetic Resonance Imaging data of heart geometry, as guides to study the nonlinear dynamics of scroll waves in our preparations. Particular attention will be given to the epicardial surface manifestation, ECG and 3-D vectorcardiographic loop pattern of reentrant activity generated by one or more scroll waves which may be established at the right or left ventricles, or even at the ventricular septum. Attention will also be given to the shape and location of the scroll filament in relation to the myocardial wall. Overall, the studies proposed here promise answers that relate importantly to the understanding of wave propagation in the heart. Moreover, achieving our goals may help to improve our ability to identify the mechanisms of life-threatening tachyarrhythmias in the diseased heart.

可能导致室性心动过速（VT）和室颤（VF） 来自心肌的漩涡状折返性兴奋。 我们的一般 假设是，在结构正常的心脏中，这些心律失常是 三维（3-D）电涡卷波激活 心脏肌肉在很高的频率。 为了验证这个假设，我们将 联合收割机使用高分辨率光学标测、心电图和 心电向量图，以及孤立的 兔哈特。 我们的研究将致力于确定 持续性单形折返性室性心动过速是静止（锚定） 涡卷波;多态VT是否是非静止涡卷的结果 波;以及VF是否是少数 非定常涡卷波 为此，我们将首先描述 Langendorff灌注心脏的电活动响应于 特定参数的变化，如温度、动作电位 时间（APD）、传导速度（CV）和基本周期长度，可能 决定了我们启动涡状再入激发的能力。 我们 然后将研究空间不均匀性的作用（即，梯度）中 涡状再入的起源和随后的演变中的APD和CV， 以及确定心律失常的类型（例如，单形或 多态性VT; VF）可能发生。 此外，我们将量化 在心室的整个心外膜表面上的螺旋波的动力学 以确定这种动力学是否与三维涡卷波一致， 可兴奋的媒介 此外，我们将使用分析工具来研究程度 波传播的空间和时间组织 t=窦性心律、心室起搏、VT和VF期间的心外膜表面。 为了研究波传播的三维方面， 研究中，我们将记录三个正交的ECG导联， 三维心电向量图环，同时获得光学标测图 整个心室表面。 最后，我们将使用一个三维“立方体” 模型，以及完整的右心室和左心室的模型， 心脏基于FitzHugh-Nagumo动力学，并基于逼真的磁 心脏几何结构的共振成像数据，作为研究非线性 在我们的准备中滚动波的动态。 将特别注意 结合心外膜表面表现、心电图及三维重建 由一个或多个心室产生的折返性活动的心电向量图环模式， 可以在右心室或左心室建立更多的涡卷波， 甚至是心室隔膜 此外，亦会留意 与心肌相关的涡卷丝的形状和位置 墙 总的来说，这里提出的研究承诺的答案， 这对理解波在心脏中的传播很重要。 此外，实现我们的目标可能有助于提高我们的识别能力， 在患病心脏中危及生命的快速性心律失常的机制。