CARDIAC ARRHYTHMIAS: MECHANISMS, DIAGNOSIS AND TREATMENT

心律失常：机制、诊断和治疗

基本信息

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
项目类别：
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

项目摘要

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.

我们的目标是增进对心脏机制的了解心律失常，这些机制可以精确控制的方式抗心律失常药物的鉴定及其作用机制允许更准确的诊断和更有效的治疗。我们选择这个区域是因为心律失常，例如通气室性心动过速和颤动是死亡的主要原因患有冠状动脉疾病或心力衰竭的个体。我们的具体目标是确定缺血和梗塞导致脑电活动的改变导致折返节律的心肌细胞，如何马戏团路径影响的功能和结构特性可折返节律及其对药物的反应以及哪些作用抗心律失常药物对于预防和终止是必要的重入激发的重刑。我们将尝试回答这些问题通过密切综合的研究来检验问题单通道缺血因子和抗心律失常药物用膜片钳方法研究单个肌细胞或用电压钳和细胞内研究全细胞电流正常心肌细胞和浦肯野细胞的透析通过使用离子的研究，急性和亚急性梗塞有所改变选择性微电极测量细胞内的变化和由旨在模仿的因素引起的细胞外成分缺血，通过微电极对正常心脏组织的研究以及因缺血和折返性研究而受损的组织犬折返模型中的心律失常和药物作用心律失常。这些模型包括两种类型的折返心房梗塞处的心律失常和室性心动过速心。最后，我们将使用一种新的光学记录方法研究室性心动过速和室颤确定电击如何终止折返和颤动节奏。