Cerebral Blood Flow Model for Normo/Hypertensive Elderly

正常/高血压老年人脑血流模型

• 批准号: 6479562
• 负责人: METTE S OLUFSEN
• 金额: $ 7.33万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-01 至 2003-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6479562
• 关键词: aging; blood pressure; body movement; brain circulation; cerebral artery; clinical research; electrocardiography; fluidity; gender difference; heart rate; human data; human old age (65+); hypertension; mathematical model; model design /development; patient oriented research; posture; ultrasonography; vascular resistance

The purpose of this investigation is to determine mechanisms of cerebrovascular autoregulation during orthostatic stress and their alterations due to aging and hypertension using a mathematical model based on principles of fluid dynamics. The specific aim is to develop a lumped parameter model that can reproduce a dynamic changes of pulsatile blood flow velocity (BFV) and pressure (BP) in the middle cerebral artery (MCA) during posture change from sitting to standing, and use this model to unravel differences in regulatory mechanisms governing cerebral blood flow (CBF) in two groups of subjects: (i) normotensive elderly subjects and (ii) elderly subjects with untreated hypertension. Extensive data on pulsatile BFV in the MCA and BP have already been gathered in Dr. Lipsitz's laboratory. We will analyze these data using the mathematical model and extract parameters, such as systemic and peripheral cerebrovascular resistance and compliance. Once differences among the groups of normotensive and untreated hypertensive subjects and between males and females have been established, we will (in a full RO1 proposal) investigate side effects related to vasodilator treatment of hypertension and effects related to vasovagal syncope. This study builds upon previous modeling work by Drs. Olufsen, Nadim, and Lipsitz, showing a biphasic cerebrovascular response to acute posture change in healthy young subjects, characterized by initial (baroreflex-mediated) vasoconstriction (and increased pulsatility), followed by autoregulatory cerebral vasodilation that restores blood flow to normal. Based on these results and preliminary observations of MCA blood flow in hypertensive subjects lack initial increase in cerebral pulsatility during posture change due to impairments in initial (baroreflex-mediated) peripheral cerebral vasoconstriction and cardioacceleration, (ii) this defect is exaggerated in untreated hypertensive elders. This work represents a unique collaboration between a clinical investigator in cardiovascular aging, Dr. Lipsitz and mathematicians specialized in modeling circulatory dynamics in branched arterial systems, Drs. Olufsen and Nadim. The proposed study responds to the goal of the RFA and helps Dr. Olufsen continue to build a successful independent research career in the important areas of cardiovascular physiology and aging.

本研究的目的是利用基于流体动力学原理的数学模型来确定直立应激时脑血管自动调节的机制及其因衰老和高血压而引起的改变。具体目的是建立一个集总参数模型，再现坐姿到站立姿势变化过程中大脑中动脉（MCA）搏动血流速度（BFV）和血压（BP）的动态变化，并利用该模型揭示两组受试者(i)血压正常的老年受试者和（ii）未治疗高血压的老年受试者脑血流量（CBF）调节机制的差异。利普西兹博士的实验室已经收集了大量关于中心动脉和BP的脉动性心电的数据。我们将使用数学模型分析这些数据，并提取参数，如全身和周围脑血管阻力和顺应性。一旦确定血压正常和未治疗高血压受试者之间以及男性和女性之间的差异，我们将（在一份完整的RO1提案中）研究血管扩张剂治疗高血压的副作用和血管迷走神经性晕厥的相关影响。这项研究建立在之前的建模工作的基础上。Olufsen， Nadim和Lipsitz的研究表明，在健康的年轻受试者中，急性体位变化表现出双相脑血管反应，其特征是初始（bar反射介导的）血管收缩（和脉搏增加），随后是自我调节的脑血管舒张，使血流恢复正常。基于这些结果和对高血压受试者MCA血流的初步观察，由于初始（barbar反射介导的）周围脑血管收缩和心脏加速的损伤，在体位改变过程中，大脑脉搏没有初始增加，（ii）这种缺陷在未经治疗的高血压老年人中被夸大。这项工作代表了心血管衰老临床研究者Lipsitz博士和专门模拟分支动脉系统循环动力学的数学家之间的独特合作。Olufsen和Nadim。拟议的研究回应了RFA的目标，并帮助Olufsen博士继续在心血管生理学和衰老的重要领域建立一个成功的独立研究生涯。