Understanding Circadian Mechanisms of Sudden Cardiac Death: A Report From the National Heart, Lung, and Blood Institute Workshop, Part 1: Basic and Translational Aspects.
Understanding Circadian Mechanisms of Sudden Cardiac Death: A Report From the National Heart, Lung, and Blood Institute Workshop, Part 1: Basic and Translational Aspects.
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DOI：
10.1161/circep.121.010181
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发表时间：
2021-11
期刊：
影响因子：
--
通讯作者：
Balijepalli RC
中科院分区：
文献类型：
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作者：
Delisle BP;George AL Jr;Nerbonne JM;Bass JT;Ripplinger CM;Jain MK;Hermanstyne TO;Young ME;Kannankeril PJ;Duffy JF;Goldhaber JI;Hall MH;Somers VK;Smolensky MH;Garnett CE;Anafi RC;Scheer FAJL;Shivkumar K;Shea SA;Balijepalli RC
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，其发生遵循不同的24小时模式。这些24小时模式可能反映了由行为、环境和/或内源性昼夜节律机制中的日/夜节律引起的致心律失常触发因素和/或心肌基质的每日变化。为了更好地解决有关昼夜节律机制的基本问题，国家心脏，肺和血液研究所召开了一个研讨会，“了解心脏性猝死的昼夜节律机制”。我们提出了一个两部分的报告，从这次研讨会的结果。第1部分总结了研讨会，并确定在基础研究和转化研究领域的研究差距和机会。所指出的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，相对于光暗周期或动物饲养温度的实验时间），这可能会损害严格性和再现性。研讨会参与者还指出，关于维持正常昼夜节律同步性的重要性以及抑郁症对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昼夜节律机制是否可以降低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小时内减轻SCD的风险。
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/or the myocardial substrate caused by day/night rhythms in behavior, the environment, and/or 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 two-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 noted was a lack of standardization in animal studies for reporting environmental conditions (e.g., 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.