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

通过周期长度阶段性变化的动态起搏重现呼吸性窦性心律失常对心律失常易感性的影响

• 批准号: MR/S021299/1
• 负责人: Alexander Carpenter
• 金额: $ 35.39万
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FS021299%2F1
• 关键词: Effects; recapitulating; respiratory; sinus; arrhythmia

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.

正常的心跳是一种电事件，通过涉及钙离子的过程触发心肌收缩。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，心率随着呼吸而增减。健康的心脏在吸气时稍微加速，呼气时稍微减慢。尽管心率随呼吸节律的周期性变化的功能优势尚不清楚，但有人认为，它可能会促进心脏泵送效率，并可能对心律具有稳定作用。这种效应在出生时就存在，在运动员中很常见，其损失强烈预测心脏骤停和死亡的风险。然而，尚不清楚心率变异性的丧失是否使心脏骤停更有可能。心脏骤停被认为是由对正常心跳的严重干扰引起的，通常是一段非常快速，不稳定的跳动，称为纤维性颤动。纤颤的机制尚未完全了解，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，即在心率中施加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，并将涉及记录单个孤立心肌细胞的电活动和钙离子变化。还将进行实验，从分离的灌注心脏中进行电记录，以确定单个细胞中不同心率的影响是否也会降低完整心脏的纤颤风险。如果假设是正确的，这项研究的信息可能对人工起搏器设备的开发非常有价值，人工起搏器设备可以恢复心率的规律变化，以降低患者的死亡风险。很大一部分心力衰竭患者接受起搏器植入术。通过对起搏器编程的细微变化，这些理解的改善可能会提高生活质量，减少心力衰竭患者的猝死，这是一个主要的健康负担。此外，我们希望提高我们对这些危险的心律的理解，并可能开辟其他新的治疗策略。

项目成果

Bilateral cardiac sympathetic denervation for refractory arrhythmia in an individual with catecholaminergic polymorphic ventricular tachycardia associated with T-cell-mediated ganglionitis.

双侧心脏去交感神经支配治疗与 T 细胞介导的神经节炎相关的儿茶酚胺能多形性室性心动过速患者的难治性心律失常。

• DOI: 10.1136/bcr-2021-244710
• 发表时间: 2022
• 期刊: BMJ case reports
• 影响因子: 0.9
• 作者: Carpenter A

Enigmatic variations: the many facets of CFTR function in the heart.

• DOI: 10.1111/apha.13525
• 发表时间: 2020-06
• 期刊: Acta physiologica
• 影响因子: 6.3
• 作者: A. James

Importance of thorough investigation in a patient presenting with recurrent collapse and ST elevation.

对反复出现虚脱和 ST 段抬高的患者进行彻底检查的重要性。

• DOI: 10.1136/bcr-2020-238057
• 发表时间: 2021
• 期刊: BMJ case reports
• 影响因子: 0.9
• 作者: Connolly GM