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

正常的心跳是一种通过钙离子引起心肌收缩的电事件。虽然有规律，但心跳并不像节拍器那样恒定。相反，在健康的情况下，心率随呼吸的变化而变化。健康的心脏在吸气时稍微加速，在呼气时稍微慢下来。虽然心率随呼吸节奏的循环变化的功能优势尚不清楚，但有人认为它可能会提高心脏泵送效率，并可能对心律有稳定作用。这种影响在出生时就存在，在运动员中很常见，它的丧失有力地预示着心脏骤停和死亡的风险。然而，目前尚不清楚心率变化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正常心跳受到严重干扰引起的，通常是一段被称为纤维性颤动的非常快速、不稳定的跳动。纤颤的机制尚不完全清楚，但涉及到心跳的异常恢复，为下一次心跳做准备。这个项目将检验这样一个假设，即施加有规律的心率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，涉及一个由科学家、外科医生和心律失常医生组成的团队，并将记录单个分离心肌细胞的电活动和钙离子的变化。实验还将对分离的、灌注的心脏进行电记录，以确定单细胞心率变化的影响是否也会降低完整的、整个心脏的纤颤风险。如果这一假设是正确的，那么这项研究的信息可能对人工起搏器的开发具有很高的价值，这些起搏器可以恢复正常的心率变化，从而降低患者的死亡风险。很大一部分心力衰竭患者接受了心脏起搏器植入。这些认识上的改进，加上对心脏起搏器程序的细微改变，可能会改善生活质量，减少心力衰竭患者的猝死，这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.