Mechanisms and Clinical Impact of Myocardial Injury Following Traumatic Brain Injury

项目总结/摘要 创伤性脑损伤（TBI）是一个主要的公共卫生问题，每年影响超过170万人 在美国严重TBI后的低血压导致脑灌注不足和临床预后不良。 大约50%的严重TBI患者接受低血压和维持脑灌注的治疗; 这可能是由于未被识别的心肌损伤和心脏功能障碍。我之前的研究表明 22%的中重度TBI患者有早期心功能不全，TBI和心脏功能不全的患者 功能障碍表现出交感神经激活的迹象，并且患有TBI和心脏功能障碍的患者经历 低血压和脑灌注不足。交感神经激活与心功能障碍有关， TBI后低血压，但机制数据有限。本提案的核心假设是， 严重的TBI通过激活交感神经系统引起心肌损伤，这导致 收缩期心功能不全，心输出量减少，低血压，脑灌注减少， 神经学结果。我们提出了3个具体目标，在严重的TBI患者：1）确定的影响，严重的TBI 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有助于心肌梗死 严重TBI后的损伤，和3）检查心肌损伤对超声心动图，血流动力学， 和严重TBI后的临床结果。这项研究的结果，以及完成一个严格的职业生涯 发展计划，将导致一个更大的试验，检查减少交感神经系统的影响， 激活对严重TBI后心肌损伤和神经系统结局的影响。我工作的长期目标是 个性化血流动力学管理和改善严重TBI后的临床结局。

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.