SUDDEN DEATH IN VENTRICULAR ARRHYTHMIAS

室性心律失常引起的猝死

• 批准号: 3330447
• 负责人: NANCY S MOISE
• 金额: $ 18.31万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-30 至 1996-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3330447
• 关键词: animal infant mortality; arrhythmia; autonomic block; autonomic disorder; disease /disorder model; dogs; electrocardiographic monitor; electrophysiology; heart innervation; heart rate; heart ventricle; immunocytochemistry; infant animal; longitudinal animal study; model design /development; sleep; sudden infant death syndrome; tachycardia; time resolved data; tyrosine 3 monooxygenase; ventricular fibrillation; videotape /videodisc

A colony of German Shepherd dogs with a syndrome that is provocatively similar to the sudden infant death syndrome (SIDS) has been established. These dogs have an inherited spontaneous ventricular arrhythmia that leads to sudden death in approximately 40% of affected dogs. The ventricular arrhythmia is exacerbated during sleep. Furthermore, most dogs with a witnessed death have died during sleep and most were 4 to 8 months of age. It is hypothesized that the arrhythmias (and death) are precipitated by an imbalance of autonomic innervation, and that this imbalance is a developmental abnormality that rectifies with advancing age. Initially, 24-hour ambulatory electrocardio-graphic (Holter) monitoring will be used to determine the temporal evolution of the spontaneous ventricular arrhythmia in affected dogs. Affected dogs also will be studied with time-lapsed video recordings during the Holter monitoring to verify the exacerbation of ventricular arrhythmias during sleep. Subsequently, electrophysiological and anatomical substrates for autonomic imbalance in the heart will be evaluated. To determine if selected electrophysiologic indices are consistent with autonomic imbalance, the corrected QT interval and heart rate variability will be compared in affected and unaffected dogs during sleep and wakefulness. Invasive electrophysiologic studies also will be used to determine if the arrhythmias can be induced with programmed-stimulation protocols with and without autonomic blockade or stimulation. To determine if selected anatomical indices are consistent with an autonomic imbalance, (123)I-labeled metaiodobenzylguanidine scintigraphy and immunocytochemical localization of tyrosine hydroxylase will be used to compare the sympathetic innervation of affected and unaffected dogs. We anticipate that this colony of German Shepherd dogs with a propensity for spontaneous ventricular arrhythmias and sudden death during sleep will serve as an unprovoked animal model of SIDS.

一群患有挑衅性综合症的德国牧羊犬 类似于婴儿猝死综合症（SIDS）的情况已经确立。 这些狗患有遗传性自发性室性心律失常，导致 大约 40% 受影响的狗突然死亡。 心室 睡眠期间心律失常会加剧。 此外，大多数狗都有 目击死亡者均是在睡眠中死亡，大多数年龄为 4 至 8 个月。 据推测，心律失常（和死亡）是由 自主神经支配的不平衡，这种不平衡是 随着年龄的增长而纠正的发育异常。 最初， 将使用24小时动态心电图（动态心电图）监测 确定自发心室的时间演变 受影响的狗出现心律失常。 受影响的狗也将接受研究 动态心电图监测期间的延时视频记录，以验证 睡眠期间室性心律失常加剧。 随后，自主神经的电生理学和解剖学基础 将评估心脏的不平衡。 判断是否被选中 电生理指标与自主神经失衡一致， 校正后的 QT 间期和心率变异性将在 受影响和未受影响的狗在睡眠和清醒时。 侵入性 电生理学研究也将用于确定是否 可以通过程序刺激方案诱发心律失常 没有自主神经阻滞或刺激。 判断是否被选中 解剖学指标与自主神经失衡一致， (123)I标记间碘苄胍闪烁扫描和免疫细胞化学 酪氨酸羟化酶的定位将用于比较 受影响和未受影响的狗的交感神经支配。 我们预计 这群德国牧羊犬有自发的倾向 室性心律失常和睡眠期间猝死将成为 无原因的 SIDS 动物模型。