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，但人们对导致猝死的确切事件序列和导致猝死的机制知之甚少。陈旧性心肌梗死、急性缺血、自主神经系统的状态、机械活性和电生理学之间存在复杂的相互作用，导致SCD并影响心动过速或心动过缓是最终的节律。在这个项目中，建议结合一套独特的技术和生理资源来研究围绕猝死的事件。一种导致自发性SCD的梗塞/缺血的动物模型正在发展中，并将以两种互补的方式进行研究。其中一组动物将配备定制开发的遥测系统，以获取清醒、可行走状态下的电生理和功能数据，消除开胸手术和麻醉以及麻醉对猝死发生率和性质的混杂影响。另一组动物将用高分辨率的三维映射来研究，以阐明导致SCD的自发性心律失常的机制。假设自主神经系统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动物突然、自发和自发死亡的预测因素，以及死亡方式。还假设自发性心动过速/纤颤最初是折返性的，陈旧性心肌梗死与心律失常的维持有关。此外，还假设心动过缓与泵衰竭有关，而不是导致低血压的迷走神经反射。建议使用这项研究的数据来开发、实施和验证在几秒到几分钟的时间尺度上预测迫在眉睫的SCD的措施。由于在没有观察到持续性心律失常的情况下，连续几天的数据采集的性质，将有可能确定衍生预测因子的特异性和敏感性。在遥测能力、心脏标测和自发性心源性猝死的新动物模型方面的创新将提供有关猝死的背景和机制的信息，这是以前所没有的。

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.