Neurobehavioral Correlates of Mental Stress Ischemia

精神应激缺血的神经行为相关性

• 批准号: 7670313
• 负责人: Robert Soufer
• 金额: $ 63.87万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7670313
• 关键词: Accounting; Affective; Anger; Area; Autonomic Pathways; Behavioral; Blood flow; Brain; Brain region; Cardiac; Cardiovascular system; Coronary heart disease; Data; Endothelin-1; Equilibrium; Event; Exercise; Functional disorder; Funding; Generations; Grant; Hostility; Image; Inflammatory; Interleukin-1; Interleukin-6; Ischemia; Joints; Laboratories; Light; Mediation; Medical; Memory; Modeling; Myocardial; Myocardial Ischemia; Myocardial perfusion; Neuraxis; Nitric Oxide; Norepinephrine; Outcome; Pathway interactions; Patients; Pattern; Peptides; Process; Property; Psyche structure; Reaction; Reflex action; Research; Research Personnel; Risk; Role; Shapes; Statistical Models; Stress; Syndrome; Testing; Tumor Necrosis Factor-alpha; Work; base; clinically relevant; cytokine; emotional factor; experience; frontal lobe; heart rate variability; improved; indexing; neurobehavioral; outcome forecast; programs; psychologic; public health relevance; response; single photon emission computed tomography; trait

DESCRIPTION (provided by applicant): The long-term objectives of our research program are to model the pathophysiology of mental stress ischemia (MSI), and to use this model to test treatments that improve prognosis for the approximately 50% of CAD patients who are at risk for poor outcomes because of this ischemic syndrome. During the current funding period we have identified a network of brain regions, including prefrontal, sub-cortical and limbic areas, that serve executive, affective, attentional, and memory functions, and that is uniquely activated during mental vs. exercise related ischemia, and during laboratory stress in patients who are dispositionally prone toward hostility and anger. We have also found that perturbations in myocardial blood flow appear necessary for the provocation of MSI. Pilot data regarding, a) laboratory stress-induced changes in autonomic balance and associated increases in levels of the inflammatory cytokine TNF-a, and, b) the potentiating effect that threshold levels of ET-1 have on sympathetic activity in the provocation of MSI, provide a direction for the articulation of a complete "neurocardiac model" of this ischemic syndrome. The aims of this proposal are to tie our observations regarding CMS activity to our observations regarding myocardial blood flow during mental stress by, 1) assessing key intermediary autonomic pathways during mental stress in patients with CAD, and 2) determining the contributions of dispositional (hostility) and reactive factors (state anger) to the provocation of ischemia during mental stress. Hypotheses relate to, a) MS induced alterations in autonomic tone, accompanying increases in levels of circulating vasoactive peptides (e.g., TNF-a, ET-1) and patterns of CMS activity during MSI; and, b) the relationship of dispositional factors to reactive factors in the prediction of MSI and the prediction of accompanying increases in levels of circulating vasoactive peptides during mental stress. Public Health Relevance: Mental stress ischemia is associated with increased risk of cardiac events and decreased survival. The complete modeling of this ischemia will help efforts to define and test treatments to reduce the risk of MSI and improve medical outcomes for patients with coronary disease.

描述（由申请人提供）：我们的研究计划的长期目标是对精神压力缺血（MSI）的病理生理学进行建模，并使用该模型测试治疗，从而改善大约50％的CAD患者预后，因为这种缺血综合征。在当前的资金期间，我们已经确定了一个大脑区域网络，包括前额叶，皮层和边缘区域，这些网络为执行，情感，注意力和记忆功能提供服务，并且在与运动相关的缺血和实验性缺血期间被引起了独特的激活，以及在对敌对性和敌对性和愤怒中处置的患者的实验性压力。我们还发现，心肌血流的扰动似乎是挑衅MSI所必需的。有关a）实验室压力诱导的自主平衡变化的试验数据以及炎症细胞因子TNF-A水平的增加，b）b）ET-1的阈值水平对MSI挑衅的交感神经活动的增强作用，为完整的“神经皮质模型”的表达提供了一个方向。该提案的目的是将我们关于CMS活性的观察结果与心理压力期间心肌血流的观察结果联系起来，1）评估CAD患者精神压力期间的关键中间自主教途径，以及2）确定处置性（敌对性）和反应性因素（态度）和反应性因素（州愤怒）的贡献。假设与a）MS诱导自主语调的改变有关，伴随着循环血管活性肽水平的增加（例如TNF-A，ET-1）以及MSI期间CMS活性的模式； b）在心理压力期间，在MSI预测和预测循环血管活性肽水平的预测中，处置因素与反应性因素的关系。公共卫生相关性：精神压力缺血与心脏事件的风险增加和生存下降有关。该缺血的完整建模将有助于努力定义和测试治疗，以降低MSI的风险并改善冠状动脉疾病患者的医疗结果。