Adaptations of Sleep and Cardiac Rhythms in the Hypometabolic State of a Human Sized Hibernator

人体大小的冬眠者代谢低下状态下睡眠和心律的适应

• 批准号: 10975413
• 负责人: Oivind Toien
• 金额: $ 15.5万
• 依托单位: UNIVERSITY OF ALASKA FAIRBANKS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10975413
• 关键词: Adaptations; Sleep; Cardiac; Rhythms; Hypometabolic

This project will leverage analysis of more than 10 years of unpublished polysomnographic recordings from long term hibernation studies in American black bears. Therapy used to decrease to decrease oxygen demands in critical care of cardiac arrest, stroke, and trauma has limited capacity without extensive use of resources, and with moderate effects, only 5-7% decrease in metabolic rate per degree of cooling. The suppression of metabolic rate during hibernation in a human sized animal model is much greater and could be clinically important if mechanisms were understood and translated to clinical use: A black bear decreases its metabolic rate by 75% during hibernation with only a moderate decrease in body temperature to 32-34°C and have still a 50% suppression of metabolic rat at 37°C during the recovery from hibernation in spring. The average heart rate decreases from about normal resting of 55 to 14 beats per minute in midhibernation, modulated by extreme cardiac sinus arrhythmia with longest inter-beat intervals more than 25 seconds. Body temperature can vary down to 30°C without apparent adverse effects on the heart, and they remain alert and can immediately respond to disturbance as opposed to the intensive care patient that typically is kept in a coma. However key information about higher brain functions and sleep/wake states during hibernation in bears is missing, and an understanding of the autonomic control required to sustain the hypometabolic state is also lacking. No previous studies have recorded blood pressure patterns in a non-anesthetized bear model during hibernation so the consequences of their low heart rate and extreme sinus arrhythmia are not known. The rationale for studying this hibernation model is that it has a physiology much closer and translatable to human physiology than deeper hibernators. 1) It will use automated sleep scoring verified against manual sleep scoring to determine the sleep patterns of bears through hibernation. The hypothesis is that hibernating bears will have a very pronounced increase in sleep time to avoid energy expenditure related to wake activity and that they suppress circadian rhythms while in the dark. The sleep patterns will be correlated with metabolic rate, and the alerting effect of body temperature levels will be determined. Frequency analysis of EEG patterns will determine if there are underlying functional differences between sleep during hibernation compared to non-hibernating state. 2) The project will further determine HR variability and blood pressure patterns in relation to metabolic state and sleep and investigate if changes in ECG

该项目将利用对10多年来未发表的多导睡眠图记录的分析 对美国黑熊进行的长期冬眠研究。用于降低至降低的治疗 心脏骤停、中风和创伤的重症监护中的氧气需求量有限， 广泛使用资源，并与中度影响，只有5-7%的代谢率下降每度 冷却。在人类大小的动物模型中，冬眠期间代谢率的抑制是非常重要的。 如果机制被理解并转化为临床用途：A 黑熊在冬眠期间代谢率降低75%，但身体仅中度下降 温度降至32-34°C，并且在恢复期间在37°C下仍具有50%的代谢抑制率 从冬眠中醒来平均心率从大约正常的55次降至14次 在冬眠中期每分钟，由具有最长间隔搏动的极端心脏窦性心律失常调制 间隔超过25秒。体温可低至30°C， 对心脏的影响，他们保持警觉，并能立即作出反应，而不是干扰 重症监护病人通常处于昏迷状态。然而关于高级大脑的关键信息 功能和睡眠/觉醒状态在冬眠期间熊是失踪，并了解 也缺乏维持低代谢状态所需的自主控制。以前的研究没有 记录了冬眠期间未麻醉熊模型的血压模式， 他们的低心率和严重窦性心律不齐的后果尚不清楚。的理由 研究这种冬眠模型的原因是，它的生理机能更接近人类， 比冬眠更深的动物1)它将使用自动睡眠评分验证对手动睡眠 来确定熊在冬眠期间的睡眠模式。假设是冬眠 熊将有一个非常显着的睡眠时间增加，以避免能源消耗有关的觉醒 活动和他们抑制昼夜节律，而在黑暗中。睡眠模式将与 与代谢率，并将确定体温水平的报警效果。频率 EEG模式的分析将确定在睡眠期间是否存在潜在的功能差异。 休眠状态与非休眠状态相比。2)该项目将进一步确定人力资源的可变性， 与代谢状态和睡眠相关的血压模式，并研究ECG变化