SUDDEN DEATH IN VENTRICULAR ARRHYTHMIAS

室性心律失常引起的猝死

基本信息

批准号：
2201430
负责人：
NANCY S MOISE
金额：
$ 20.48万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1991
资助国家：
美国
起止时间：
1991-09-30 至 1998-08-31
项目状态：
已结题

项目摘要

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.

一个综合症的德国牧羊犬的殖民地与突然的婴儿死亡综合征（SID）相似。这些狗有一个遗传的自发性心律失常，导致大约40％受影响的狗突然死亡。心室在睡眠期间，心律不齐会加剧。此外，大多数狗都有见证死亡在睡眠期间死亡，大多数年龄在4到8个月大。假设心律不齐（和死亡）是由自主神经的失衡，这种失衡是发展异常随着年龄的增长而纠正。最初，将使用24小时的心理心电图（Holter）监测确定自发性心室的时间演变受影响的狗的心律失常。受影响的狗还将研究在Holter监视期间，时间范围的视频录制以验证睡眠期间心室心律失常的加剧。随后，自主神经的电生理和解剖基板将评估心脏不平衡。确定是否选择电生理指数与自主性失衡一致，校正的QT间隔和心率可变性将在在睡眠和清醒期间影响和未受影响的狗。侵入性电生理研究还将用于确定是否是否心律不齐可以通过和和没有自主性封锁或刺激。确定是否选择解剖学指数与自主性失衡一致，（123）i标记的metaiododobenzylguanidine闪烁显像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同情神经。我们期待那个有自发倾向的德国牧羊犬的殖民地心室心律失常和睡眠期间的猝死将作为小岛屿发展中国家的动物模型。