Aging and Heart Failure are not Similar Syndromes of Sympathetic Dysregulation

衰老和心力衰竭并不是类似的交感神经失调综合征

• 批准号: 7665576
• 负责人: Michael J Kenney
• 金额: $ 18.25万
• 依托单位: KANSAS STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7665576
• 关键词: Acute; Admission activity; Affect; Age; Aging; American; Case Study; Chronic; Congestive Heart Failure; Diagnosis; Disease; Elderly; Epidemic; Epinephrine; Exercise; Fever; Glare; Heart failure; Hepatic; Homeostasis; Hospitalization; Human; Incidence; Individual; Kidney; Left Ventricular Dysfunction; Maintenance; Mediating; Nerve; Patients; Pattern; Persons; Physiological; Play; Population; Prevalence; Rattus; Regulation; Rest; Rodent Model; Role; Stress; Sympathetic Nervous System; Syndrome; Testing; Time; Trauma; acute stress; age effect; age related; aged; aging population; base; blood flow measurement; design; evidence base; healthy aging; natural hypothermia; neural circuit; programs; response; stressor; thermal stress

DESCRIPTION (provided by applicant): Despite recent advances in the diagnosis and treatment of heart failure (HF), the incidence of this disorder is increasing, primarily due to the aging of the population. HF is primarily a pathological disorder of the aged, with prevalence rates increasing from less than 1% in individuals younger than 50 years to about 10% in individuals older than 80 years. The combined impact of an aging population and age-related distribution of HF have increased the incidence of this disease to epidemic proportions. The sympathetic nervous system plays a crucial role in the regulation of physiological homeostasis under basal conditions and in response to acute and chronic stressors. Although sympathetic dysregulation is considered a hallmark of both HF and aging, not a single study has determined the effect of aging on sympathetic nerve discharge (SND) responses to acute stress in young and old rats with the same degree of left ventricular dysfunction and congestive HF, despite evidence demonstrating diversity in mechanisms regulating physiological responses in aging and HF. This is a significant omission as a reduced ability of the sympathetic nervous system to respond to acute stress may be an important reason why both aged individuals and HF patients are less able to adapt to trauma and physical exercise, and perform normal daily activities. The long-term objectives of this application are to understand alterations in SND responses to acute stress in aged rats with and without accompanying HF. The proposed studies will, for the first time, advance the hypothesis that aging and HF represents dissimilar syndromes of altered sympathetic nervous system regulation. Using direct nerve recordings and blood flow measurements the current proposal is designed to investigate the following Specific Aim: Determine the effect of advancing age, with and without the imposing pathological condition of congestive HF, on sympathetic nerve responses to acute environmental stress. The specific hypothesis to be tested is that aging and HF are not similar syndromes of sympathetic nervous system dysregulation, as evidenced by differences in the responsiveness of sympathetic neural circuits to acute stress (hyperthermia and hypothermia) in young compared with aged HF rats and in aged HF compared with aged sham HF rats. The lack of foundational evidence demonstrating the validity of current rodent models for studying the combined effect of aging and HF on sympathetic nerve regulation is a glaring omission, especially when it is known that the HF syndrome in older adults differs from that in younger patients. PUBLIC RELEVANCE: The sympathetic nervous system is responsible for maintenance of physiological homeostasis at rest and in response to stressors; however, sympathetic dysregulation is a hallmark of aging and heart failure, a pathophysiological state primarily affecting the aged. Despite this the result of aging on sympathetic nerve discharge responses to acute stress in the aged heart-failure state is unknown, but may provide rationale why both aged and HF individuals are less able to perform normal daily activities or adequately adapt to physical exercise programs. Thus, the current study is designed to determine the effects of advanced aged, with and without heart failure, on the ability of the sympathetic nervous system to respond to acute stress.

描述（由申请人提供）：尽管心力衰竭（HF）的诊断和治疗最近取得了进展，但这种疾病的发病率正在增加，主要是由于人口老龄化。HF主要是老年人的病理性疾病，患病率从50岁以下个体的不到1%增加到80岁以上个体的约10%。人口老龄化和与年龄相关的HF分布的综合影响使该疾病的发病率增加到流行比例。交感神经系统在基础条件下以及对急性和慢性应激源的反应中在生理稳态的调节中起着至关重要的作用。虽然交感神经失调被认为是HF和衰老的标志，但没有一项研究确定了衰老对具有相同程度左心室功能障碍和充血性HF的年轻和老年大鼠对急性应激的交感神经放电（SND）反应的影响，尽管有证据表明衰老和HF中调节生理反应的机制存在差异。这是一个重要的遗漏，因为交感神经系统对急性应激反应的能力降低可能是老年人和HF患者适应创伤和体育锻炼以及进行正常日常活动的能力降低的重要原因。本申请的长期目标是了解伴有和不伴有HF的老年大鼠对急性应激的SND反应的改变。拟议的研究将首次提出这一假设，即衰老和HF代表交感神经系统调节改变的不同综合征。使用直接的神经记录和血流测量，目前的建议是为了调查以下具体目标：确定年龄增长的影响，有和没有强加的病理条件充血性HF，交感神经对急性环境压力的反应。待检验的具体假设是，衰老和HF不是交感神经系统失调的相似综合征，如年轻HF大鼠与老年HF大鼠以及老年HF大鼠与老年假HF大鼠相比交感神经回路对急性应激（高温和低温）的反应性差异所证明的。缺乏基础证据证明当前啮齿动物模型用于研究衰老和HF对交感神经调节的联合作用的有效性是一个明显的遗漏，特别是当已知老年人的HF综合征与年轻患者不同时。公众相关性：交感神经系统负责在休息时和响应于应激源维持生理稳态;然而，交感神经失调是衰老和心力衰竭的标志，这是一种主要影响老年人的病理生理状态。尽管如此，老年心力衰竭状态下交感神经放电对急性应激反应的老化结果尚不清楚，但可以提供老年人和HF个体进行正常日常活动或充分适应体育锻炼计划的能力较低的理由。因此，目前的研究旨在确定老年人（有或无心力衰竭）对交感神经系统对急性应激反应能力的影响。

项目成果

Effects of combined aging and heart failure on visceral sympathetic nerve and cardiovascular responses to progressive hyperthermia in F344 rats.

衰老和心力衰竭联合对 F344 大鼠内脏交感神经和心血管对进行性高热反应的影响。

• DOI: 10.1152/ajpregu.00434.2010
• 发表时间: 2010
• 期刊: American journal of physiology. Regulatory, integrative and comparative physiology
• 作者: Margiocco,ML;Borgarelli,M;Musch,TI;Hirai,DM;Hageman,KS;Fels,RJ;Garcia,AA;Kenney,MJ
• 通讯作者: Kenney,MJ