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Central Autonomic Nervous System Regulation in Heart Failure

心力衰竭中枢自主神经系统调节

基本信息

批准号：
8551705
负责人：
Rajesh Kumar
金额：
$ 40.03万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-27 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8551705
关键词：
Affect Age American Angiotensins Area Arrhythmia Autonomic nervous system Baroreflex Blood Pressure Brain Brain Injuries Brain region Bypass Cardiac Cerebellar cortex structure Cerebellum Characteristics Congenital neurologic anomalies Development Diffusion Magnetic Resonance Imaging Evaluation Exhibits Functional Magnetic Resonance Imaging Future Gender Handedness Heart failure Hypothalamic structure Imaging Techniques Injury Insula of Reil Intervention Laboratories Learning Left Link Mediating Morbidity - disease rate Movement Nature Nervous System Physiology Neuraxis Neurology Newly Diagnosed Output Patients Peripheral Process Quality of life Reaction Recovery Regulation Relative (related person)Renin Research Right-On Risk Side Signal Transduction Site Stroke Structure Symptoms Testing Time Tissues Valsalva Maneuver brain tissue comparative design high risk improved injured innovation mortality novel therapeutics patient population regenerative response

项目摘要

DESCRIPTION (provided by applicant): The objective is to determine how damaged brain autonomic nervous system (ANS) regulatory areas (hypothalamus, insula cortex, and cerebellum) respond to an ANS challenge, and to assess the laterality of functional responses to that challenge in heart failure (HF) subjects. Abnormal autonomic nervous system activity in HF is associated with increased morbidity and mortality. It is unclear if the structural damage seen in central ANS control regions reflects functional ANS abnormalities. Our preliminary studies found that injury in ANS control regions was accompanied by lateralized, altered (blunted, inverted, or time-delayed) functional deficits to ANS challenges in HF, and these changes preferentially occurred on the right side. The lateralization of damage and impaired functional responses on the right-side can increase risk for cardiac dysrhythmias and increase ANS abnormalities. However, responses of these damaged brain regions to ANS challenges are unclear, and the extent to which the lateralized injury contributes to abnormal ANS reactivity in HF has yet to be described. Therefore, using a two-group comparative design, we will examine the structural integrity in brain ANS control areas using diffusion tensor imaging procedures and functional responses and laterality of those signal changes to an ANS challenge using functional magnetic resonance imaging (MRI) procedures in 40 HF and 40 age- and gender-matched healthy controls. The specific aims are to:1) evaluate functional responses to an ANS challenge eliciting sequential sympathetic and parasympathetic actions (Valsalva maneuver) in a set of ANS regulatory brain regions (hypothalamus, insular cortices, and cerebellum) using functional MRI procedures in HF and healthy controls; 2) evaluate the relationships between structural integrity (using diffusion tensor imaging procedures) and functional activity (via functional MRI) of brain regions which regulate ANS tone in HF subjects. These studies will aid in the identification, development, and evaluation of new therapeutic strategies to protect and retrain central nervous system regions to restore ANS function, and improve survival and quality of life in this high risk patient population. Potential future interventions for these structural and functional ANS abnormalities could include peripheral or centrally-acting pharmacologic agents (such as statins or angiotensin-renin blockers), or neuroprotective interventions, including retraining/reorganization of alternative brain structures to restore ANS brain functions.