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Understanding Circadian Mechanisms of Sudden Cardiac Death: A Report From the National Heart, Lung, and Blood Institute Workshop, Part 1: Basic and Translational Aspects
Circulation: Arrhythmia and Electrophysiology ( IF 8.4 ) Pub Date : 2021-11-01 , DOI: 10.1161/circep.121.010181
Brian P Delisle 1 , Alfred L George 2 , Jeanne M Nerbonne 3 , Joseph T Bass 4 , Crystal M Ripplinger 5 , Mukesh K Jain 6 , Tracey O Hermanstyne 7 , Martin E Young 8 , Prince J Kannankeril 9 , Jeanne F Duffy 10 , Joshua I Goldhaber 11 , Martica H Hall 12 , Virend K Somers 13 , Michael H Smolensky 14 , Christine E Garnett 15 , Ron C Anafi 16 , Frank A J L Scheer 17 , Kalyanam Shivkumar 18 , Steven A Shea 19 , Ravi C Balijepalli 20
Affiliation  

Sudden cardiac death (SCD), the unexpected death due to acquired or genetic cardiovascular disease, follows distinct 24-hour patterns in occurrence. These 24-hour patterns likely reflect daily changes in arrhythmogenic triggers and the myocardial substrate caused by day/night rhythms in behavior, the environment, and endogenous circadian mechanisms. To better address fundamental questions regarding the circadian mechanisms, the National Heart, Lung, and Blood Institute convened a workshop, Understanding Circadian Mechanisms of Sudden Cardiac Death. We present a 2-part report of findings from this workshop. Part 1 summarizes the workshop and serves to identify research gaps and opportunities in the areas of basic and translational research. Among the gaps was the lack of standardization in animal studies for reporting environmental conditions (eg, timing of experiments relative to the light dark cycle or animal housing temperatures) that can impair rigor and reproducibility. Workshop participants also pointed to uncertainty regarding the importance of maintaining normal circadian rhythmic synchrony and the potential pathological impact of desynchrony on SCD risk. One related question raised was whether circadian mechanisms can be targeted to reduce SCD risk. Finally, the experts underscored the need for studies aimed at determining the physiological importance of circadian clocks in the many different cell types important to normal heart function and SCD. Addressing these gaps could lead to new therapeutic approaches/molecular targets that can mitigate the risk of SCD not only at certain times but over the entire 24-hour period.

中文翻译:

了解心源性猝死的昼夜节律机制:来自国家心肺血液研究所研讨会的报告,第 1 部分:基本和转化方面

心源性猝死 (SCD) 是由于获得性或遗传性心血管疾病导致的意外死亡,其发生率具有不同的 24 小时模式。这些 24 小时模式可能反映了由行为、环境和内源性昼夜节律机制中的昼夜节律引起的心律失常触发因素和心肌底物的每日变化。为了更好地解决有关昼夜节律机制的基本问题,国家心肺血液研究所召开了一次研讨会,名为“了解心源性猝死的昼夜节律机制”。我们提交了一份由两部分组成的本次研讨会的调查结果报告。第 1 部分总结了研讨会,并确定了基础研究和转化研究领域的研究差距和机会。差距之一是在报告环境条件的动物研究中缺乏标准化(例如,相对于光暗循环或动物住房温度的实验时间),这可能会损害严谨性和可重复性。研讨会参与者还指出了维持正常昼夜节律同步的重要性以及不同步对 SCD 风险的潜在病理影响的不确定性。提出的一个相关问题是是否可以针对昼夜节律机制来降低 SCD 风险。最后,专家们强调需要进行旨在确定生物钟在对正常心脏功能和 SCD 很重要的许多不同细胞类型中的生理重要性的研究。解决这些差距可能会导致新的治疗方法/分子靶点,不仅可以在某些时间,而且可以在整个 24 小时内降低 SCD 的风险。
更新日期:2021-11-17
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