The Impact of Cardiovascular Funcfion on Stroke Outcome

心血管功能对卒中结果的影响

• 批准号: 9313284
• 负责人: Paul D Chantler
• 金额: $ 29.45万
• 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/9313284
• 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; Cerebrovascular Disorders; Cerebrum; Clinical Management; Clinical Treatment; Contralateral; Coronary Arteriosclerosis; Data; Development; Dyslipidemias; Echocardiography; Evaluation; Event; Functional disorder; Goals; Health Care Costs; Heart; Human; Hypertension; Impairment; Infarction; Insulin Resistance; Ischemic Stroke; Left; Left Ventricular Dysfunction; Left Ventricular Ejection Fraction; Left Ventricular Function; Life; Location; Measures; Mentors; Microvascular Dysfunction; Middle Cerebral Artery Occlusion; Modeling; Motor; Neurological status; Obesity; Operative Surgical Procedures; Outcome; Patients; Perfusion; Phase; Physiological; Play; Radio; Recording of previous events; Recovery; Risk Factors; Rodent; Rodent Model; Role; Savings; Severities; Stroke; Structure; Subarachnoid Hemorrhage; Techniques; Telemetry; Testing; Therapeutic; Thinness; Time; Training; United States National Institutes of Health; Ventricular; West Virginia; X-Ray Computed Tomography; Zucker Rats; cerebral microvasculature; cognitive testing; density; disability; effective therapy; experience; experimental study; functional disability; functional outcomes; improved; in vivo; in vivo imaging; outcome forecast; post stroke; 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/location, and history of cardiovascular disease (CVD, coronary artery disease, hypertension etc). There is a critical need to improve upon existing approaches used in the evaluation and therapeutic 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 of the integrated CV response, i.e., the ability of the autonomic nervous system to adjust arterial and cardiac function, 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 patients shortly after onset of AIS followed by 30-day post-AIS evaluation of functional 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 translational 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 patients. We will incorporate in-vivo and ex-vivo assessments of CV structure/function before, and post AIS. Our analogous studies in humans and rodents provide an optimal 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.

急性缺血性中风 (AIS) 相关残疾的严重程度变化很大，并且被认为取决于 年龄、梗塞面积/位置以及心血管疾病史（CVD、冠状动脉疾病、高血压 ETC）。迫切需要改进评估和治疗中使用的现有方法 管理 AIS 以降低 AIS 相关残疾。心血管（CV）系统在 中风后结果的严重程度，因为主动脉僵硬度（AS）和交感神经活动的增加是中风后结局的预测因素 中风结果。此外，了解综合 CV 反应，即自主神经的能力 神经系统调节动脉和心脏功能，维持梗死区充足的脑灌注 区域，可能会增强我们预测不良 AIS 结果的能力。然而，评估急性发作的效用 AIS 事件期间 AS、心脏功能和自主控制的变化可作为卒中结果的预测因子 或尚未检查推荐的立即治疗。我们的近期目标是检查 AIS 期间发生的生理变化可作为中风结果的潜在救生预测因子， AIS 急性治疗的潜在目标。具体来说，我们将测量自主神经和CV的变化 患者在 AIS 发病后不久进行 30 天的功能结果评估（改良版） 兰金）。与此同时，我们将在一个实验中测量与手术引起的 AIS 类似的生理变化。 CVD 啮齿动物模型，肥胖 Zucker 大鼠 (OZR)。 OZR 是 CVD 的优秀转化模型 源于肥胖、胰岛素抵抗、血脂异常和中度肥胖的过度饮食发展 高血压。许多 CVD 危险因素在中风患者中都很明显。我们将结合体内和 AIS 之前和之后的 CV 结构/功能的体外评估。我们对人类的类似研究 啮齿动物提供了剖析导致中风的病理生理机制的最佳机会 患者的结果。这些数据将增进我们对中风的 CV 反应的理解，并提供 为改善中风临床治疗奠定基础。这种方法可能有助于缓解不断上涨的医疗保健费用 预计到 2030 年，脑血管疾病造成的费用将达到 8180 亿美元。