Chronic monitoring of ischemic models of sudden death

大多数心脏性猝死（SCD）与冠状动脉疾病有关，但对导致心脏性猝死的确切事件顺序和机制知之甚少，陈旧性心肌梗死、急性缺血、自主神经系统状态、机械活力和电生理之间存在复杂的相互作用，这些因素导致SCD并影响心动过速或心动过缓是否为最终心律。在这个项目中，建议将联合收割机一套独特的技术和生理资源结合起来，研究围绕猝死的事件。导致自发性SCD的梗死/缺血动物模型一直在开发中，并将以两种互补的方式进行研究。一组动物将配备定制开发的遥测系统，以在清醒、非卧床状态下采集电生理和功能数据，消除开胸术和麻醉以及麻醉对猝死发生率和性质的混杂影响。将对另一组动物进行高分辨率三维标测研究，以阐明导致SCD的自发性心律失常的机制。据推测，自主神经系统的迷走神经和交感神经臂之间的平衡和心肌复极特性的变化是哪些动物突然自发死亡和自发死亡以及死亡模式的预测因子。还假设自发性心动过速/纤颤最初是折返性的，并且陈旧性梗死参与心律失常维持。此外，假设心动过缓与泵衰竭相关，而不是迷走神经反射导致低血压。建议使用本研究的数据来开发，实施和验证在秒到分钟的时间尺度上预测即将发生的SCD的措施。由于数据采集的连续性超过几天，当没有观察到持续的心律失常，它将有可能确定的特异性以及衍生的预测的灵敏度。遥测能力、心脏标测和自发性心脏性猝死的新动物模型方面的创新将提供以前没有的关于猝死背景和机制的信息。

Most sudden cardiac death (SCD) is associated with coronary artery disease, but little is known about the exact sequence of events that leads up to it and the mechanisms responsible for it. There is a complex interplay between old myocardial infarcts, acute ischemia, the status of the autonomic system, mechanical viability, and electrophysiology that leads to SCD and influences whether tachycardia or bardycardia is the final rhythm. In this project, it is proposed to combine a unique set of technological and physiological resources to study the events surrounding sudden death. An animal model of infarct/ischemia leading to spontaneous SCD has been developing and will be studied in two complementary ways. One set of animals will be instrumented with a custom-developed telemetry system to acquire electrophysiologic and functional data during the conscious, ambulatory state, eliminating the confounding effects of thoracotomy and anesthesia and anesthesia on the incidence and nature of sudden death. Another set of animals will be studied with high resolution, three dimensional mapping to elucidate the mechanisms of the spontaneous arrhythmias that lead to SCD. It is hypothesized that the balance between the vagal and sympathetic arms of the autonomic system and that changes in repolarization properties of the myocardium are predictors of which animals die suddenly and spontaneously and spontaneously as well as the mode of death. It is also hypothesized that spontaneous tachycardia/fibrillation is initially reentrant and that the old infarct is involved in the arrhythmia maintenance. Further, it is hypothesized that bradycardia is associated with pump failure rather than a vagal reflex leading to hypotension. It is proposed to use the data from this research to develop, implement and validate measures that predict imminent SCD on the time scale of seconds to minutes.. Because of the continuous nature of data acquisition over several days when no sustained arrhythmias are observed, it will be possible to determine the specificity as well as the sensitivity of derived predictors. Innovations in telemetry capability, cardiac mapping, and new animal models of spontaneous sudden cardiac death will provide information about the context and mechanisms of sudden death that has not been available before.