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: 7531335
• 负责人: Michael J Kenney
• 金额: $ 21.9万
• 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 2010-05-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7531335
• 关键词: Acute; Admission activity; Affect; Age; Aging; American; Case Study; Chronic; Condition; Congestive Heart Failure; Daily; 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; Rate; 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; healthy aging; hyperthermia treatment; 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）：尽管最近在心力衰竭（HF）的诊断和治疗方面取得了进展，但这种疾病的发病率正在增加，主要是由于人口老龄化。心衰主要是一种老年人的病理性疾病，患病率从50岁以下人群的不到1%上升到80岁以上人群的10%左右。人口老龄化和HF的年龄相关分布的综合影响使该病的发病率增加到流行病的程度。交感神经系统在基础条件下的生理稳态调节和对急性和慢性应激源的反应中起着至关重要的作用。尽管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的年轻和年老大鼠交感神经放电（SND）对急性应激反应的影响，尽管有证据表明衰老和HF的生理反应调节机制存在差异。这是一个重要的遗漏，因为交感神经系统对急性应激反应能力的降低可能是老年人和心衰患者无法适应创伤和体育锻炼以及无法进行正常日常活动的重要原因。这项应用的长期目标是了解老年大鼠SND对急性应激反应的变化，伴有和不伴有心衰。提出的研究将首次提出衰老和HF代表交感神经系统调节改变的不同综合征的假设。通过直接神经记录和血流测量，本研究旨在研究以下具体目标：确定年龄增长对交感神经对急性环境应激反应的影响，无论是否伴有充血性心力衰竭的病理状态。需要验证的具体假设是，衰老和心衰不是交感神经系统失调的相似综合征，这一点可以通过年轻HF大鼠与老年HF大鼠相比，老年HF大鼠与老年假性HF大鼠相比，交感神经回路对急性应激（热疗和低温疗）的反应差异来证明。目前研究衰老和心衰对交感神经调节的联合影响的啮齿动物模型的有效性缺乏基础证据，这是一个明显的缺失，特别是当我们知道老年人的心衰综合征不同于年轻患者时。公共相关性：交感神经系统在休息和应激时负责维持生理稳态；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，在老年心力衰竭状态下，衰老对交感神经放电反应的影响尚不清楚，但可能提供了老年人和心力衰竭患者无法进行正常日常活动或充分适应体育锻炼计划的原因。因此，目前的研究旨在确定老年患者，无论有无心力衰竭，对交感神经系统对急性压力的反应能力的影响。