REPOLARIZATION VARIABILITY AND SUDDEN CARDIAC DEATH

复极变异性和心源性猝死

• 批准号: 2392769
• 负责人: Ronald D Berger
• 金额: $ 10.62万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-04-20 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2392769
• 关键词: arrhythmia; clinical research; dogs; electrocardiography; heart electrical activity; heart rate; heart rhythm; human subject; intraluminal angioplasty; myocardium disorder; sudden cardiac death

DESCRIPTION (adapted from the applicant's abstract): The central hypothesis of this proposal is that abnormal beat-to-beat fluctuations in ventricular repolarization occur in close association with malignant arrhythmias and that quantification of these fluctuations provides a noninvasive measure of electrical instability. The proposed studies will make use of an automated technique to measure subtle beat-to-beat QT interval variability (QTV) from the surface electrocardiogram. Physiologic QTV in normal dogs and normal human volunteers will be quantified, and the relationship between normal heart rate variability and QTV will be established. The effect of dilated cardiomyopathy (DCM) on QTV will then be examined both in an established dog model of DCM and in patients with DCM. Two fundamental issues regarding the underlying mechanisms of QTV will be addressed. First, is increased QTV with DCM due to diffuse or localized repolarization lability? To answer this question, spatially disparate data will be acquired invasively in dogs with monophasic action potential recordings obtained at multiple endocardial sites, and noninvasively in humans by use of 12 simultaneous surface ECG leads. Second, is QTV mediated by the autonomic nervous system? QTV will be measured both in patients with DCM and those with structurally normal hearts undergoing electrophysiologic study, during sinus rhythm and during atrial pacing, before and after pharmacologic autonomic blockade, to test the hypothesis that QTV is autonomically mediated in the absence of structural heart disease but becomes decoupled from autonomic control in DCM. The final set of proposed studies are designed to test the effect of acute metabolic abnormalities on the QTV. The QTV will be measured in dogs with DCM during progressive hypokalemia, and in humans undergoing percutaneous transluminal coronary angioplasty (PTCA) during ischemia induced by balloon inflation. These studies will test the hypothesis that repolarization lability accompanies and may herald the onset of malignant ventricular arrhythmias brought about by an abnormal metabolic state.

描述(改编自申请人的摘要)：中央 这一提议的假设是异常的节拍波动 发生在心室复极与恶性肿瘤密切相关 心律失常和这些波动的量化提供了一种 电气不稳定性的非侵入性测量。建议进行的研究 将利用自动化技术来测量微妙的节拍 体表心电图QT间期变异性(QTV)。 正常犬和正常人类志愿者的生理性QTV 量化，以及正常心率变异性之间的关系 并将建立QTV。扩张型心肌病的影响 在QTV上将在DCM和DCM的已建立的狗模型中进行检查 在扩张型心肌病患者中。关于基础的两个基本问题 将对QTV的机制进行探讨。首先，是通过DCM增加QTV 是由于弥漫性还是局部性复极化不稳定？要回答这个问题 问题：在狗身上，空间上不同的数据将被侵入性地获取 单相动作电位记录在多个频率下获得 心内膜部位，并在人类中同时使用12个无创 体表心电图导联。第二，QTV是由自主神经介导的吗 系统？QTV将在扩张型心肌病患者和 接受电生理学研究的结构正常的心脏 窦性心律和心房起搏时的药理学前后 自主神经阻断，以检验QTV是自主的假设 在没有结构性心脏病的情况下调节，但成为 在DCM中与自主控制解耦。最后一套建议的 研究旨在测试急性代谢异常的影响。 在QTV上。QTV将在进展期在患有扩张型心肌病的狗身上进行测量 低钾血症，以及接受经皮冠状动脉腔内治疗的人 血管成形术(PTCA)在球囊充气诱导的缺血期间。这些 研究将检验复极化不稳定的假设 伴随并可能预示着恶性脑室的发病 由不正常的代谢状态引起的心律失常。