Mechanisms and Clinical Impact of Myocardial Injury Following Traumatic Brain Injury

脑外伤后心肌损伤的机制和临床影响

基本信息

批准号：
9816144
负责人：
Vijay Krishnamoorthy
金额：
$ 18.89万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-15 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9816144
关键词：
Address Adrenergic Receptor Adult Affect Autonomic Dysfunction Autonomic nervous system Baroreflex Blood Pressure Brain Cardiac Cardiac Output Cardiovascular system Catecholamines Cerebral Ischemia Cerebrovascular Circulation Cerebrum Cessation of life Clinical Clinical Management Clinical Trials Clinical Trials Design Control Groups Data Development Development Plans Emergency department visit Epidemiology Exhibits Functional disorder Gene Expression Glasgow Coma Scale Glasgow Outcome Scale Goals Guidelines Heart Hospitalization Hour Hypotension Impairment Incidence Individual Injury International K-Series Research Career Programs Knowledge Low Cardiac Output Lymphocyte Maintenance Mediating Mentors Motion Myocardial Myocardial dysfunction Nervous System Physiology Neurologic Neurological outcome Orthopedics Outcome Pathway interactions Patient Care Patient-Focused Outcomes Patients Perfusion Plasma Prospective cohort study Public Health Research Resources Role Sympathetic Nervous System TBI Patients Training Support Traumatic Brain Injury Troponin T United States University Hospitals Work Workload career development cerebral hypoperfusion experience heart function heart rate variability hemodynamics human data improved personalized intervention preservation prevent programs

项目摘要

PROJECT SUMMARY/ABSTRACT Traumatic brain injury (TBI) is a major public health concern, affecting more than 1.7 million individuals annually in the United States. Hypotension after severe TBI results in cerebral hypoperfusion and poor clinical outcomes. Approximately 50% of severe TBI patients are treated for hypotension and maintenance of cerebral perfusion; this may be due to unrecognized myocardial injury and cardiac dysfunction. My prior research has demonstrated that: 22% of patients with moderate-severe TBI have early cardiac dysfunction, patients with TBI and cardiac dysfunction exhibit signs of sympathetic activation, and patients with TBI and cardiac dysfunction experience hypotension and cerebral hypoperfusion. Sympathetic activation is implicated in cardiac dysfunction and hypotension after TBI, but mechanistic data is limited. The central hypothesis of the current proposal is that severe TBI causes myocardial injury through activation of the sympathetic nervous system, and this results in systolic cardiac dysfunction, reduced cardiac output, hypotension, decreased cerebral perfusion, and poor neurologic outcomes. We propose 3 Specific Aims in patients with severe TBI: 1) Determine the effect of severe TBI on autonomic nervous system function, 2) Determine if autonomic dysfunction contributes to myocardial injury after severe TBI, and 3) Examine the impact of myocardial injury on echocardiographic, hemodynamic, and clinical outcomes after severe TBI. Results of this study, as well as completion of a rigorous career development plan, will lead to a larger trial that examines the impact of reduction of sympathetic nervous system activation on myocardial injury and neurologic outcomes after severe TBI. The long-term goal of my work is to personalize hemodynamic management and improve clinical outcomes after severe TBI.

项目概要/摘要创伤性脑损伤 (TBI) 是一个重大的公共卫生问题，每年影响超过 170 万人在美国。严重 TBI 后的低血压会导致脑灌注不足和不良的临床结果。大约 50% 的严重 TBI 患者因低血压和维持脑灌注而接受治疗；这可能是由于未被识别的心肌损伤和心功能障碍所致。我之前的研究表明表明：22%的中重度TBI患者有早期心功能不全，TBI患者合并心脏功能障碍功能障碍表现出交感神经激活的迹象，患有 TBI 和心脏功能障碍的患者会经历低血压和脑灌注不足。交感神经激活与心脏功能障碍有关 TBI 后出现低血压，但机制数据有限。当前提案的中心假设是严重的 TBI 通过激活交感神经系统导致心肌损伤，从而导致收缩性心功能不全、心输出量减少、低血压、脑灌注减少、心功能差神经系统结果。我们对严重 TBI 患者提出 3 个具体目标： 1) 确定严重 TBI 的影响 TBI 对自主神经系统功能的影响，2) 确定自主神经功能障碍是否会导致心肌病严重 TBI 后的损伤，以及 3) 检查心肌损伤对超声心动图、血流动力学、以及严重 TBI 后的临床结果。这项研究的结果，以及严格的职业生涯的完成开发计划，将导致更大规模的试验，检查交感神经系统减少的影响严重 TBI 后心肌损伤和神经系统结果的激活。我工作的长期目标是个性化血流动力学管理并改善严重 TBI 后的临床结果。