CARDIAC ARRHYTHMIAS: MECHANISMS, DIAGNOSIS AND TREATMENT

心律失常：机制、诊断和治疗

• 批准号: 2216648
• 负责人: BRIAN F HOFFMAN
• 金额: $ 144.19万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-01-01 至 1994-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2216648
• 关键词: antiarrhythmic agent; arrhythmia; cellular pathology; electrophysiology; heart disorder diagnosis; heart pharmacology; myocardial infarction; myocardial ischemia /hypoxia

Our goal is to improve understanding of the mechanisms for cardiac arrhythmias, the ways in which these mechanisms can be precisely identified and the mechanisms of action of antiarrhythmic drugs to permit more accurate diagnosis and more effective treatment. We have selected this area because cardiac arrhythmias such as vent- ricular tachycardia and fibrillation are the major cause of death in individuals with coronary artery disease or heart failure. Our specific aims are to determine the mechanisms by which ischemia and infarction bring about alterations in the electrical activity of cardiac cells that lead to reentrant rhythms, how both the functional and structural properties of the circus path influence reentrant rhythms and their responses to drugs and which actions of antiarrhythmic drugs are necessary for prevention and termina- tion of reentrant excitation. We will attempt to answer these questions by closely integrated studies examining the effects of ischemic factors and antiarrhythmic drugs on single channel currents studied with patch-clamp methods in single myocytes or whole-cell currents studied with voltage-clamp and intracellular dialysis in both normal myocardial and Purkinje cells and those modified by acute and subacute infarction, by studies using ion selective microelectrodes to measure alterations in intracellular and extracellular composition caused by factors designed to mimic ischemia, by studies with microelectrodes on normal cardiac tissues and tissues damaged by ischemia and by studies on reentrant arrhythmias and drug actions in canine models of reentrant arrhythmias. These models include two types of reentrant atrial arrhythmias and also ventricular tachycardia in the infarcted heart. Finally, we will use a new optical recording method to study ventricular tachycardia and ventricular fibrillation and determine how electrical shocks terminate reentry and fibrillatory rhythms.

我们的目标是提高对心脏机制的理解 心律不齐，这些机制可以精确的方式 鉴定和抗心律失常药物的作用机理 允许更准确的诊断和更有效的治疗方法。 我们 之所以选择该区域，是因为心律不齐（例如通风口） ricular心动过速和纤颤是主要的死亡原因 在患有冠状动脉疾病或心力衰竭的个体中。 我们的 具体目的是确定缺血和 梗塞会改变 导致恢复节奏的心脏细胞，两者如何 马戏路径的功能和结构特性 再入节奏及其对毒品的反应以及哪些行动 抗心律失常药物的预防和末期是必需的 恢复激励的影响。 我们将尝试回答这些 通过紧密整合研究的问题检查 单个通道上的缺血因素和抗心律失常药物 用单个肌细胞中的补丁钳方法研究的电流或 用电压钳和细胞内研究的全细胞电流 正常心肌和浦肯野细胞中的透析以及 通过使用离子进行研究，通过急性和亚急性梗塞修饰 选择性微电极以测量细胞内的改变 由设计模仿的因素引起的细胞外组成 缺血，通过对正常心脏组织上的微电脱模的研究 和缺血损害的组织以及对重入的研究 重入犬模型中的心律失常和药物作用 心律不齐。 这些模型包括两种类型的重入房屋 心律不齐和心室心动过速 心。 最后，我们将使用一种新的光学记录方法 研究心室心动过速和心室纤颤和 确定电击如何终止重新进入和纤颤 节奏。