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

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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.