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）：尽管心力衰竭的诊断和治疗最近进步（HF），但这种疾病的发生率正在增加，这主要是由于人群的老龄化。 HF主要是一种老年病理性障碍，患病率从小于50岁以下的个体中的1％增加到80岁以上的人的10％。老龄化人口的综合影响和与年龄相关的HF分布增加了这种疾病的发病率对流行比例的率。交感神经系统在基础条件下的生理稳态调节以及响应急性和慢性应激源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，但并非一项研究确定了衰老对年龄段（SND）对急性压力的影响（SND）对急性压力的反应，尽管有证据表明在调节生理学反应的机制方面具有多样性，但具有相同程度的左心室功能障碍和交流性HF的急性压力。这是一个很大的遗漏，因为交感神经系统应对急性压力的能力降低可能是老年人和HF患者都无法适应创伤和体育锻炼并进行正常日常活动的重要原因。本应用程序的长期目标是了解具有和不伴随HF的老年大鼠中SND对急性压力的反应的改变。拟议的研究将首次推进衰老和HF代表改变交感神经系统调节的不同综合症的假设。使用直接的神经记录和血流测量结果目前的建议旨在研究以下特定目的：确定促进年龄的影响，在有或没有充满充血HF的病理状况的情况下，对急性环境压力的交感神经反应。要测试的特定假设是，与年龄HF大鼠相比，与年龄的HF相比，与年轻的HF大鼠相比，衰老和HF并不是交感神经系统失调的综合症，这证明了交感神经回路对急性压力（高热和体温过低）的反应性的差异所证明。缺乏基本证据表明，目前啮齿动物模型研究衰老和HF对交感神经调节的综合作用的有效性是一个明显的遗漏，尤其是当知道老年人的HF综合征与年轻患者的HF综合征有所不同时。公众相关性：交感神经系统负责维持静止的生理体内平衡并应对压力源； however, sympathetic dysregulation is a hallmark of aging and heart failure, a pathophysiological state primarily affecting the aged.尽管如此，在老年心失事状态下对急性压力的交感神经排出反应老化的结果尚不清楚，但可能会提供理由，为什么老年人和HF个体都无法进行正常的日常活动或足够适应体育锻炼计划。因此，当前的研究旨在确定高级老年人（或没有心力衰竭）对交感神经系统应对急性压力的能力的影响。