Chronobiology of cardiovascular and pulmonary disease

心血管和肺部疾病的时间生物学

• 批准号: 7120052
• 负责人: STEVEN A SHEA
• 金额: $ 12.58万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 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 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7120052
• 关键词: behavior test; biomarker; bioperiodicity; cardiovascular disorder; cardiovascular disorder risk; circadian rhythms; clinical research; electrocardiography; electroencephalography; electromyography; electrooculography; hemodynamics; hemostatics; human subject; psychophysiology; respiratory disorder; sleep; statistics /biometry; stressor; wakefulness

DESCRIPTION (provided by applicant): The applicant has a funded research program in medical chronobiology, and is the Associate Director of an NIH funded Harvard-wide Training Program in Sleep, Circadian & Respiratory Neurobiology. He has a track record and commitment to mentoring clinical researchers. The candidate's immediate goal is to determine the physiological mechanisms underlying the robust day/night pattern in adverse cardiovascular events, and of nocturnal asthma. The long-term goal is to develop a group of outstanding clinical investigators studying complementary aspects of medical chronobiology. A K24 award will enable the applicant to realize these goals by enabling him to relinquish his clinical duties in a sleep disorders program and allowing more protected time for both patient-oriented research and mentoring of clinical research fellows. The environment for this research is outstanding, with over 50 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 a General Clinical Research Center. The candidate has funding to determine the role of the body clock versus sleep in causing nocturnal asthma. The candidate plans to extend these studies in asthma, and to perform parallel studies into the mechanisms underlying the day-night pattern of adverse cardiovascular events, which has a large peak around 9 AM. To this end, 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 pulmonary and cardiovascular risk markers of (1) the intrinsic circadian rhythm (independent from behaviors); (2) the pattern in behavior related to the sleep-wake cycle, posture and activity (controlling for circadian phase); (3) any interaction. The biomarkers with potential relevance to cardiovascular vulnerability will include hemodynamic, hemostatic, autonomic and endothelial function measures. The applicant's longer-term goals will be to improve therapy in such disorders via modifications in behavior or chronopharmacology.

描述（由申请人提供）： 该申请人拥有一项资助的医学年度生物学研究计划，并且是NIH资助的哈佛大学范围内培训计划的副主任。他有记录和致力于指导临床研究人员的承诺。候选人的近期目标是确定不良心血管事件和夜间哮喘中强大日夜模式的生理机制。长期的目标是开发一组杰出的临床研究人员，研究医学表年生物学的互补方面。 K24奖项将使申请人能够通过使他在睡眠障碍计划中的临床职责中实现这些目标，并为以患者为导向的研究和对临床研究成员的指导提供更多保护的时间。这项研究的环境非常出色，有50多名成功的研究教师参与了哈佛范围内的睡眠医学部门。有“艺术状态”研究设施，包括一般临床研究中心的密集生理监测套件。候选人有资金来确定身体时钟与睡眠在引起夜间哮喘中的作用。候选人计划将这些研究扩展到哮喘中，并对不良心血管事件的日夜模式进行平行研究，该机制在上午9点左右具有很大的峰值。为此，将使用“强制性脱离”方案，其中受试者的行为在昼夜循环的所有阶段发生。目的是确定（1）固有的昼夜节律（独立于行为）对肺和心血管风险标志的影响； （2）与睡眠效果周期，姿势和活动相关的行为模式（控制昼夜节相）； （3）任何相互作用。与心血管脆弱性潜在相关的生物标志物将包括血流动力学，造血，自主和内皮功能测量。申请人的长期目标将是通过修改行为或年流制药的修改来改善此类疾病的治疗。