Ventricular Fibrillation in a Globally Ischemic Heart: From Cell to ECG

全球缺血性心脏中的心室颤动：从细胞到心电图

• 批准号: 7749558
• 负责人: ALEXEY V ZAITSEV
• 金额: $ 33.86万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-01-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7749558
• 关键词: Action Potentials; Affect; Animals; Area; Blood; Blood flow; Calcium; Cardiac; Cardiopulmonary Resuscitation; Cells; Coupled; Coupling; Data; Diffuse; Electric Countershock; Electrocardiogram; Electrodes; Electrophysiology (science); Equilibrium; Event; Evolution; Future; Glass; Goals; Grant; Heart; Heart Arrest; Hemorrhage; Hospitals; In Situ; Ischemia; Lead; Link; Maps; Measurement; Measures; Mechanics; Methods; Microscopic; Modality; Morphologic artifacts; Motion; Muscle Cells; Myocardial Ischemia; Nature; Needles; Optics; Pattern; Periodicity; Phase; Physiological; Preparation; Principal Investigator; Publications; Published Comment; Reporting; Research; Research Personnel; Resolution; Risk; Role; Shapes; Signal Transduction; Simulate; Site; Solutions; Specificity; Structure; Suction; Surface; System; Techniques; Time; Tissues; Translating; Ventricular; Ventricular Fibrillation; Writing; base; blood pump; heart cell; innovation; novel strategies; prevent; programs; research study; restraint; spatiotemporal; sudden cardiac death; tool

DESCRIPTION (provided by applicant): The broad, long-term goal of the proposed project is to provide a rational basis for the treatment of ventricular fibrillation (VF), a major cause of sudden cardiac death. The onset of VF causes the heart to stop pumping blood, which leads to ischemia (the lack of the blood flow) in the body and in the heart itself. Prolonged ischemia alters the cardiac state in such a way that it makes most of the attempts of defibrillation and cardio-pulmonary resuscitation futile. Empirical evidence indicates that the structure of VF ECG waveform is predictive of survival. The nature of this connection remains unknown. However, the ECG waveform reflects the spatiotemporal organization of electrical wavelets which sustain VF. Therefore, understanding the mechanisms linking the spatiotemporal organization of VF to ischemia is a necessary step towards determining the factors of survival, especially after prolonged times of VF/ischemia. Here we propose to use a combination of single cell, whole heart, and whole animal studies to establish a link between ischemia-specific alterations of cellular electrophysiology, spatiotemporal dynamics of fibrillatory waves, and the ECG waveform. The overall hypothesis is that the ischemia-induced changes in the balance between inward and outward currents, as well as in the coupling between the action potential and intracellular calcium cycling, lead to a dynamic instability in the action potential shape. This instability translates into a progressive disorganization of propagating wavelets and explains the progressive loss of periodicity in the ECG waveform. The specific aims are: 1. To analyze the mechanisms of dynamic instabilities of the action potential and Ca transient in isolated ventricular myocytes subjected to simulated conditions of ischemic VF. 2. To analyze mechanisms whereby dynamic instabilities of the AP and Ca transient cause conduction abnormalities during simulated and real ischemic VF in the whole heart. 3. To establish the link between the temporal regularity of the action potential, the dynamics of propagating wavelets and the ECG during natural VF evolution in-situ. Ventricular fibrillation (VF) is major cause of sudden cardiac death. The proposed research should explain physiological mechanisms linking the changes in the electrical activity during VF to the arrest of blood flow in the heart. It should also provide a scientific basis for the interpretation of VF ECG. This should help to optimize defibrillation and cardio-pulmonary resuscitation in the setting of out-of-hospital sudden cardiac arrest.

描述（由申请人提供）：拟议项目的广泛长期目标是为心室纤颤（VF）的治疗提供合理的基础，这是心脏突然死亡的主要原因。 VF的发作导致心脏停止抽血，从而导致体内和心脏本身缺血（缺乏血液流动）。长时间的缺血改变了心脏状态，使其大部分尝试进行除颤和心肺复苏的尝试徒劳无功。经验证据表明，VF ECG波形的结构可预测生存。这种联系的性质仍然未知。但是，心电图波形反映了维持VF的电波的时空组织。因此，了解将VF的时空组织与缺血联系起来的机制是确定生存因素的必要步骤，尤其是在VF/缺血时间长时间之后。在这里，我们建议使用单细胞，全心和全动物研究的组合，以在细胞电生理学的缺血特异性变化，纤颤波的时空动力学和ECG波形之间建立联系。总体假设是缺血诱导的内向电流和外部电流之间的平衡以及动作电位和细胞内钙循环之间的耦合导致动作电位形状的动态不稳定性。这种不稳定性转化为传播小波的进行性混乱，并解释了ECG波形中的周期性逐渐丧失。具体目的是：1。分析动作电位的动态不稳定性的机制和CA瞬时在受缺血性VF的模拟条件下的分离室心肌细胞中。 2。分析机制，通过该机制，在整个心脏中，AP和CA瞬态的动态不稳定性会导致模拟和真实缺血性VF期间导致传导异常。 3。为了建立动作电位的时间规律性之间的联系，在天然VF进化过程中，传播小波的动力学和ECG的动力学。心室纤颤（VF）是心脏猝死的主要原因。拟议的研究应解释将VF期间电活动变化与心脏中血流阻止联系起来的生理机制。它还应该为解释VF ECG提供科学依据。这应该有助于在心脏外突出心脏骤停的情况下优化除颤和心肺复苏。