Chronobiology of cardiovascular and pulmonary disease

心血管和肺部疾病的时间生物学

• 批准号: 8318642
• 负责人: STEVEN A SHEA
• 金额: $ 18.01万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-20 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8318642
• 关键词: Adrenergic beta-Antagonists; Adverse event; Affect; Age; Aging; Arousal; Asthma; Autonomic nervous system; Behavior; Behavior Therapy; Behavioral; Bicycling; Biological; Biological Clocks; Biological Markers; Blood Platelets; Blood Pressure; Blood Vessels; Body Temperature; Cardiac; Cardiovascular Diseases; Cardiovascular system; Center for Translational Science Activities; Cerebrovascular Circulation; Cerebrum; Cessation of life; Chronobiology; Circadian Rhythms; Clinical; Clinical Investigator; Clinical Sciences; Disease; Elderly; Environment; Epidemiologic Studies; Epidemiology; Epinephrine; Equilibrium; Event; Exercise; Exertion; Exhibits; Faculty; Frequencies; Funding; Future; Goals; Heart Diseases; Heart Rate; Hemostatic Agents; Homeostasis; Hospitals; Hour; Human; Hydrocortisone; Hypothalamic structure; Impedance Cardiography; Individual; Intervention; Jet Lag Syndrome; Laboratories; Lead; Life Style; Lung diseases; Measures; Medical; Medicine; Melatonin; Mentors; Modification; Myocardial Infarction; Neurobiology; Neurocognitive; Neurons; Obesity; Outcome; Pattern; Pharmaceutical Preparations; Phase; Physiologic Monitoring; Physiological; Physiological Adaptation; Play; Population; Posture; Protocols documentation; Psyche structure; Regulation; Research; Research Personnel; Risk Factors; Risk Marker; Role; Schedule; Secondary to; Severities; Severity of illness; Site; Sleep; Sleep Wake Cycle; Societies; Stress; Stroke; Structure; System; Therapy Clinical Trials; Time; Tissues; Training Programs; United States; United States National Institutes of Health; Universities; Variant; Ventricular Arrhythmia; Vulnerable Populations; Woman; Work; age effect; base; behavior influence; cardiovascular disorder therapy; cardiovascular risk factor; circadian behavioral rhythms; circadian pacemaker; clinically relevant; density; hemodynamics; improved; mortality; primary outcome; programs; research facility; research study; respiratory; response; secondary outcome; sedentary; shift work; stressor; sudden cardiac death; suprachiasmatic nucleus

The applicant has a funded research program in medical chronoblology, is Associate Director of an NIH funded Harvard-wide Training Program in Sleep, Circadian & Respiratory Neurobiology, and has an excellent track record and commitment to mentoring clinical researchers using where appropriate the formal structure provided by this Training Program. The candidate's goal is to develop a group of outstanding clinical investigators of medical chronoblology - to understand the circadian and sleep/wake mechanisms underlying the day/night pattern in the severity of a number of disorders. The environment for this research is outstanding, with over 60 successful research faculty involved with the Harvard-wide Division of Sleep Medicine. There are 'state of the art' research facilities, comprising intensive physiological monitoring suites in Harvard University's Clinical and Translational Science Center (CTSC) at the Brigham & Women's Hospital site. The candidate has current research funding to determine the role of the body clock versus behaviors on cardiovascular risk markers in healthy young subjects. To understand the clinical relevance of this work, the candidate wishes to extend these studies to examine more vulnerable populations, such as elderly, sedentary, obese and hypertensive individuals. In these groups, epidemiological studies have revealed a high frequency of adverse cardiovascular events around 10 AM. To study such effects, a "Forced Desynchrony" protocol will be used, wherein subjects' behaviors occur at all phases of the circadian cycle. The aims are to determine the effect upon cardiovascular risk markers of the intrinsic circadian rhythm (independent from behaviors) and any interaction between the circadian system and behavioral stressors, including postural changes, exercise and mental stress. Cardiovascular markers of vulnerability include autonomic nervous system measures, cerebral blood flow autoregulation, platelet aggregability and endothelial function. It is anticipated that standard behavioral stressors (standardized changes in posture, activity or sleep/wake state) will have different effects at specific phases of the circadian cycle - revealing vulnerable phases of the circadian system for certain behaviors. The applicant's longer term goals will be to improve therapy in such disorders via modifications in behavior or chronopharmacology.

申请人拥有医学年代学的资助研究项目，是美国国立卫生研究院资助的哈佛睡眠、昼夜节律和呼吸神经生物学培训项目的副主任，拥有出色的记录，并承诺在适当情况下使用该培训项目提供的正式结构来指导临床研究人员。应聘者的目标是培养一批杰出的医学年代学临床研究人员--了解昼夜节律和睡眠/觉醒机制在一些疾病的严重程度中的潜在作用。这项研究的环境非常好，有60多名成功的研究人员参与了哈佛大学睡眠医学部。在哈佛大学位于布里格姆和妇女医院的临床和翻译科学中心(CTSC)，有一套最先进的研究设施，包括密集的生理监测套件。这位候选人目前拥有研究资金，以确定健康年轻受试者的生物钟与心血管风险标记物上的行为之间的作用。为了了解这项工作的临床相关性，候选人希望将这些研究扩展到更脆弱的人群，如老年人、久坐不动的人、肥胖和高血压患者。在这些人群中，流行病学研究显示，上午10点左右发生不良心血管事件的频率很高。为了研究这种影响，我们将使用一种“强制去同步化”方案，即受试者的行为发生在生理周期的所有阶段。其目的是确定内在昼夜节律(独立于行为)以及昼夜节律系统和行为应激源之间的任何交互作用对心血管风险标记物的影响，包括姿势变化、运动和精神应激。易损性的心血管标志物包括自主神经系统指标、脑血流自动调节、血小板聚集性和内皮功能。预计标准的行为应激源(姿势、活动或睡眠/清醒状态的标准化变化)将在昼夜节律的特定阶段产生不同的影响-揭示某些行为的昼夜节律系统的脆弱阶段。申请者的长期目标将是通过改变行为或时间药理学来改善此类疾病的治疗。