The Impact of Cardiovascular Funcfion on Stroke Outcome

心血管功能对卒中结果的影响

• 批准号: 8663440
• 负责人: Paul D Chantler
• 金额: $ 25.45万
• 依托单位: WEST VIRGINIA UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8663440
• 关键词: Acute; Address; Affect; Age; Aorta; Area; Autonomic nervous system; Baroreflex; Blood Pressure; Brain; Cardiac; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Cerebral Infarction; Cerebral Ischemia; Cerebrovascular Circulation; Cerebrum; Clinical Management; Clinical Treatment; Cognitive; Contralateral; Coronary Arteriosclerosis; Data; Development; Dyslipidemias; Echocardiography; Evaluation; Event; Goals; Health Care Costs; Heart; Human; Hypertension; Infarction; Insulin Resistance; Ischemic Stroke; Left; Left Ventricular Dysfunction; Left Ventricular Function; Life; Measures; Mentors; Microvascular Dysfunction; Middle Cerebral Artery Occlusion; Modeling; Motor; Neurological status; Obesity; Outcome; Patients; Perfusion; Phase; Physiological; Play; Radio; Recording of previous events; Recovery; Risk Factors; Rodent; Rodent Model; Role; Severities; Stroke; Structure; Subarachnoid Hemorrhage; Techniques; Telemetry; Testing; Time; Training; United States National Institutes of Health; Vascular Diseases; Ventricular; West Virginia; X-Ray Computed Tomography; Zucker Rats; base; density; disability; effective therapy; experience; functional disability; functional outcomes; improved; in vivo; in vivo imaging; outcome forecast; post stroke; research study; response; skills; standard of care; stem; stroke recovery; tonometry

The severity of the acute ischemic stroke (AIS) related disability is highly variable, and thought to depend on age, infarct size/locafion, and history of cardiovascular disease (CVD, coronary artery disease, hypertension etc). There is a critical need to improve upon existing approaches used in the evaluafion and therapeufic management of AIS to lower AIS related disability. The cardiovascular (CV) system plays a critical role in the severity of post stroke outcome, as increased aortic stiffness (AS) and sympathetic activity are predictors of stroke outcome. Further, an understanding ofthe integrated CV response, i.e., the ability ofthe autonomic nervous system to adjust arterial and cardiac funcfion, to maintain adequate cerebral perfusion to the infarct area, may enhance our ability to predict poor AIS outcomes. However, the utility of assessing the acute changes in AS, cardiac function, and autonomic control during an AIS event as a predictor of stroke outcome or recommended immediate treatment has not been examined. Our immediate goal is to examine the physiological changes that occur during AIS as potential life-saving predictors of stroke outcome and potential targets for acute therapy with AIS. Specifically, we will measure autonomic and CV changes in pafients shortly after onset of AIS followed by 30-day post-AIS evaluafion of funcfional outcome (modified Rankin). In parallel we will measure comparable physiological changes with surgically-induced AIS in a rodent model of CVD, the obese Zucker rat (OZR). The OZR is an excellent translafional model of CVD stemming from its hyperphagic development of obesity, insulin resistance, dyslipidemia and moderate hypertension. Many of these CVD risk factors are evident in stroke pafients. We will incorporate in-vivo and ex-vivo assessments of CV structure/funcfion before, and post AIS. Our analogous studies in humans and rodents provide an opfimal opportunity to dissect pathophysiological mechanisms that contribute to stroke outcome in patients. These data will advance our understanding of the CV responses to stroke and provide the basis for improved clinical management of stroke. This approach may help alleviate the rising healthcare costs of cerebral vascular disease, projected to be $818 billion by 2030.

急性缺血性卒中（AIS）相关残疾的严重程度是高度可变的，并被认为取决于 年龄、梗死面积/部位和心血管疾病（CVD、冠状动脉疾病、高血压）史 等等）。迫切需要改进现有的评估和治疗方法。 治疗AIS以降低AIS相关残疾。心血管（CV）系统在心脏病中起着关键作用。 卒中后结局的严重程度，因为主动脉僵硬度（AS）和交感神经活动增加是 卒中结局。此外，理解综合CV反应，即，自主能力 神经系统调节动脉和心脏功能，以维持足够的脑灌注到梗死 这可能会提高我们预测AIS不良结局的能力。然而，评估急性 AIS事件期间AS、心功能和自主控制的变化作为卒中结局的预测因素 或建议的立即治疗尚未检查。我们的近期目标是检查 AIS期间发生的生理变化作为卒中结局的潜在救生预测因子， AIS急性治疗的潜在靶点。具体来说，我们将测量自主神经和CV的变化， AIS发作后不久，对患者进行AIS后30天的功能结局评价（改良 兰金）。与此同时，我们将测量与实验诱导的AIS相当的生理变化， CVD的啮齿动物模型，肥胖Zucker大鼠（OZR）。OZR是CVD的一个很好的模型 源于其肥胖、胰岛素抵抗、血脂异常和中度 高血压许多这些CVD危险因素在中风患者中是明显的。我们将在体内和 AIS之前和之后CV结构/功能的离体评估。我们对人类的类似研究， 啮齿类动物提供了一个最好的机会，解剖病理生理机制，有助于中风 患者的结局。这些数据将促进我们对中风的CV反应的理解， 改善中风临床管理的基础。这种方法可能有助于缓解不断上升的医疗保健 脑血管疾病的成本，预计到2030年将达到8180亿美元。