REPOLARIZATION VARIABILITY AND SUDDEN CARDIAC DEATH

复极变异性和心源性猝死

• 批准号: 2901214
• 负责人: Ronald D Berger
• 金额: $ 11.97万
• 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/2901214
• 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 该建议的假设是， 在心室复极发生与恶性 心律失常和量化这些波动提供了一个 电不稳定性的非侵入性测量。 拟议的研究 将利用自动化技术来测量细微的心跳 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QTV将被 量化，和正常心率变异性之间的关系， QTV将成立。 扩张型心肌病（DCM） 然后将在已建立的DCM犬模型和 在DCM患者中。 两个基本问题， 将讨论QTV的机制。 首先，是增加QTV与DCM 由于弥漫性或局部复极化不稳定性？ 回答这个 问题，空间上完全不同的数据将在狗中侵入性地获得 通过在多个时间点获得单相动作电位记录， 内分泌部位，并通过使用12个同时 体表心电图导联。 QTV是否由自主神经介导 系统中？ QTV将在DCM患者和 结构正常的心脏进行电生理学研究，在 窦性心律和心房起搏期间，药物治疗前后 自主神经阻滞，以检验QTV是神经性的假设， 在没有结构性心脏病的情况下介导， 与DCM中的自主控制分离。 最后一组建议 研究旨在测试急性代谢异常的影响， 在QTV。 将在进行性扩张型心肌病犬中测量QTV 低钾血症，以及接受经皮腔内冠状动脉成形术的人 在由球囊膨胀引起的缺血期间进行血管成形术（PTCA）。 这些 研究将检验复极不稳定性 伴随并可能预示着恶性心室 由不正常的新陈代谢状态引起的心律失常。