Aging and Heart Failure are not Similar Syndromes of Sympathetic Dysregulation

点击翻译按钮获取中文摘要

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.