EFFECTS/EXERCISE/ENDOTHELIAL FUNCTION IN STROKE PATIENTS

对中风患者的影响/运动/内皮功能

• 批准号: 7092140
• 负责人: Frederick M. Ivey
• 金额: $ 12.93万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-15 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7092140
• 关键词: aerobic exercise; aging; biological signal transduction; cardiovascular disorder risk; cardiovascular function; clinical research; fibrinolysis; glucose metabolism; human middle age (35-64); human old age (65+); human subject; hyperinsulinism; insulin sensitivity /resistance; nitric oxide; stroke; vascular endothelium; vasomotion

DESCRIPTION (provided by applicant): Candidate: Frederick M. Ivey, Ph.D. is an Assistant Professor in the Division of Gerontology, School of Medicine at the University of Maryland, Baltimore. The long-term career goal of the candidate is to advance academically in a research environment focusing on stroke, exercise, insulin-glucose metabolism, and cardiovascular risk factor modification. Dr. Ivey has recently joined the faculty in the Division, making this the ideal time in his career for this RCA to provide advanced research training in clinical and laboratory investigation. The candidate's immediate goat is to examine the mechanisms by which exercise afibcts atherothrombotic risk in chronic hemiparetic stroke patients under the guidance of experienced mentors. Background: Stroke is the leading cause of disability and thkd leading cause of death in the United States. Physical inactivity following stroke increases the incidence of hyperinsulinemia and the insulin resistance syndrome, which increases risk for recurrent stroke and MI by impairing endogenous fibrinoiysis and vasomotor function. Current strategies for preventing recurrent stroke and M1 are limited. Although aerobic exercise (AEX) improves fibrinolysis, nitric oxide-related vasomotor reactivity (NO-VMR), and insulin sensitivity in the healthy elderly, no prior studies have addressed the effects of AEX therapy on vascular endothelial celt function and insulin-glucose metabolism in chronic hemiparetic stroke patients. Our preliminary data provides the first evidence of improved endogenous fibrinolysis and reduced hyperinsulinemia in chronic hemiparetic stroke patients with AEX training. Hypothesis: In the proposed RCA the candidate investigates the hypothesis that 6 months treadmill AEX improves endogenous fibrinolysis and nitric oxide-related VMR in chronic hemiparetic stroke patients, and that these changes are related to improved insulin mediated glucose metabolism on both the whole body and tissue levels. The specific aims are to: 1) Determine the effects of 6 months AEX on a) fibrinolysis profiles and b) NO-VMR in the cerebral circulation. 2) Determine the effects of AEX on whole body insulin action, and whether alterations in fibrinolysis and NO-VMR are related to exercise-induced changes in insulin levels and action 3) Determine the effects of hemiparesis and AEX on insulin signaling proteins in stroke skeletal muscle. Environment: The Division of Gerontology has excellent resources for advanced research training in aging, stroke, exercise, metabolic, and vascular research. Additional training in molecular medicine is facilitated by Drs. Shuldiner and McLenithan, co-mentors on the revised proposal.

描述（由申请人提供）： 候选人：Frederick M. Ivey，博士是巴尔的摩马里兰大学医学院老年学系的助理教授。候选人的长期职业目标是在专注于中风、运动、胰岛素-葡萄糖代谢和心血管危险因素修正的研究环境中取得学术进步。 Ivey 博士最近加入了该部门，这使其成为他职业生涯中为该 RCA 提供临床和实验室研究高级研究培训的理想时机。候选人的当务之急是在经验丰富的导师的指导下研究运动降低慢性偏瘫中风患者动脉粥样硬化血栓形成风险的机制。背景：在美国，中风是导致残疾的主要原因，也是导致死亡的主要原因。中风后缺乏身体活动会增加高胰岛素血症和胰岛素抵抗综合征的发生率，从而损害内源性纤维蛋白溶解和血管舒缩功能，从而增加中风复发和心肌梗死的风险。目前预防中风和 M1 复发的策略有限。尽管有氧运动（AEX）可以改善健康老年人的纤溶、一氧化氮相关血管舒缩反应性（NO-VMR）和胰岛素敏感性，但之前没有研究探讨AEX治疗对慢性偏瘫卒中患者血管内皮细胞功能和胰岛素-葡萄糖代谢的影响。我们的初步数据提供了通过 AEX 训练改善慢性偏瘫卒中患者内源性纤维蛋白溶解和降低高胰岛素血症的第一个证据。假设：在拟议的 RCA 中，候选人研究了这样的假设：6 个月的跑步机 AEX 改善了慢性偏瘫中风患者的内源性纤维蛋白溶解和一氧化氮相关的 VMR，并且这些变化与改善胰岛素介导的全身和组织水平的葡萄糖代谢有关。具体目标是： 1) 确定 6 个月 AEX 对 a) 纤维蛋白溶解曲线和 b) 脑循环中 NO-VMR 的影响。 2) 确定 AEX 对全身胰岛素作用的影响，以及纤溶和 NO-VMR 的变化是否与运动引起的胰岛素水平和作用的变化有关 3) 确定偏瘫和 AEX 对中风骨骼肌中胰岛素信号蛋白的影响。环境：老年学部拥有针对衰老、中风、运动、代谢和血管研究方面的高级研究培训的优质资源。博士促进了分子医学的额外培训。 Shuldiner 和 McLenithan，修订提案的共同导师。