Effects of recapitulating respiratory sinus arrhythmia by dynamic pacing with phasically varying cycle length on susceptibility to cardiac arrhythmia

正常的心跳是一种电子事件，通过涉及钙离子的过程触发心肌收缩。心跳虽然有规律，但并不像节拍器那样持续不变。相反，在健康状态下，心率随着呼吸的变化而变化。健康的心跳在吸气时略有加快，呼气时略有减慢。虽然心率随呼吸节律的周期性变化的功能优势尚不清楚，但已有研究表明，它可能会提高心泵的效率，并可能对心率起到稳定作用。这种影响在出生时就存在，在运动员中很常见，它的缺失强烈地预测了心脏骤停和死亡的风险。然而，目前尚不清楚心率变异的丧失是否会增加心脏骤停的可能性。心脏骤停被认为是由于对通常有规律的心跳造成的重大干扰，通常是一段非常快、不稳定的心跳，称为纤颤。纤颤的机制尚不完全清楚，但涉及心跳的异常恢复，为下一次心跳做准备。这个项目将检验这样一个假设，即在心率上施加有规律的变化可以防止引发纤颤的过程。这项研究使用了布里斯托尔大学建立的技术和专业知识，由科学家、外科医生和心律失常医生组成的团队参与，将记录单个分离心肌细胞的电活动和钙离子的变化。还将进行实验，对分离的、灌流的心脏进行电子记录，以确定单个细胞中不同心率的影响是否也能降低完整心脏的纤颤风险。如果假设是正确的，这项研究的信息很可能对开发人工心脏起搏器设备具有很高的价值，这种设备可以恢复心率的规则变化，以降低患者的死亡风险。相当大比例的心力衰竭患者接受了起搏器植入。通过对起搏器编程的细微改变，这些认识上的改进可能会提高生活质量，减少心力衰竭患者的猝死，心力衰竭是一种主要的健康负担。此外，我们希望提高我们对这些危险心律的理解，并有可能开辟其他新的治疗策略。

The normal heartbeat is an electrical event that triggers contraction of heart muscle through a process involving calcium ions. Although regular, the heartbeat is not constant like a metronome. Rather, in health, the heart rate waxes and wanes in time with breathing. The healthy heart speeds up slightly with inhalation and slows down slightly with exhalation. Although the functional advantage of the cyclic variation in heart rate with breathing rhythm is unclear, it has been suggested that it may occur to promote heart pumping efficiency and may have a stabilising effect on the heart rhythm. The effect is present at birth, is common in athletes and its loss strongly predicts the risk of cardiac arrest and death. However, it is not known whether the loss of variation of heart rate makes cardiac arrest more likely. Cardiac arrest is thought to be caused by a major disturbance to the usual regular heartbeat, often a period of very rapid, erratic beating called fibrillation. The mechanisms of fibrillation are not fully understood but involve abnormal recovery of the heartbeat in preparation for the next heartbeat. This project will examine the hypothesis that imposing regular variation in the heart rate prevents the processes that initiate fibrillation. The research uses techniques and expertise established at the University of Bristol, involving a team of scientists, surgeons and arrhythmia doctors and will involve recordings of electrical activity and of changes in calcium ions in single isolated heart muscle cells. Experiments will also be conducted to make electrical recordings from isolated, perfused-hearts to establish whether the effects of varying heart rate in single cells also reduce risk of fibrillation in intact, whole hearts. If the hypothesis is correct, the information from this study is likely to be highly valuable to the development of artificial pacemaker devices that restore regular variation in heart rate to reduce risk of death in patients. A significant proportion of patients with heart failure undergo pacemaker implantation. These improvements in understanding could potentially, with subtle changes to pacemaker programming, improve quality of life and reduce sudden death for patients living with heart failure, a major health burden. In addition we hope to improve our understanding of these dangerous heart rhythms and potentially open up other novel treatment strategies.