Primate Model of Hypertensive Cerebrovascular Disease

灵长类高血压脑血管病模型

• 批准号: 6547879
• 负责人: RONALD J KILLIANY
• 金额: $ 8.08万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6547879
• 关键词: Macaca mulatta; aorta; aorta obstruction; bioengineering /biomedical engineering; biomedical equipment development; blood pressure; brain; cerebrovascular disorders; clinical research; dementia; disease /disorder model; hypertension; implant; male; mature animal; medical implant science; model design /development; neuropathology; pathologic process; pathology; perfusion; psychological aspect of aging; telemetry; tissue /cell preparation

Within the next twenty years, 50% of all individuals in this country will be 50 years old or older, an aging time point that has been characterized in cross sectional data by the onset of cognitive decline. This shifting of the population to a proportionately greater number of older individuals has fueled concerns about the effects of aging and age-related diseases and their relationship to cognitive decline. One of the most common conditions affecting individuals as they age is hypertension, the incidence of which is 25% among all adults in the US., and greater than 50% among all adults over the age of 65. At present, this condition affects over 60 million people in the U S alone, of whom it is estimated 50% may be untreated. Moreover, evidence has accumulated to show convincingly that hypertension, in addition to aging, produces impairment in multiple domains of cognitive function, even at mildly elevated levels of blood pressure. In addition, hypertension is a major risk factor for cerebrovascular dementia which alone accounts for approximately 20% of all dementia and likely contributes to another 15% to 20% of the dementia cases. However, the mechanism by which hypertension induces neuropathological changes is poorly understood, in part because only limited animal models exist for studying these processes. The purpose of this project is to test a novel device for inducing hypertension in the non-human primate. The device is surgically implanted into the chest of the monkey surrounding the thoratic arota. The device can be adjusted externally to narrow the diameter of the arota (but not fully constricting it) resulting in increased blood flow and hypertension to the upper limbs and head. By adjusting the device gradually over a period of time, the blood pressure can be raised gradually until hypertension is induced. We will test this device in non-survival and short-term survival situations in five monkeys. They will be continuously monitored for blood pressure, body temperature, EKG and activity using radiotelemetry devices and values compare from pre-implant to post-implant levels. Finally, as part of a preliminary effort to understand the mechanism by which neuropatholoigical processes are induced in the brain, we will survey the brain and aorta for signs of pathology.

在接下来的20年里，这个国家50%的人将达到50岁或50岁以上，这是一个老龄化的时间点，在横断面数据中，这一时间点的特点是认知能力开始下降。这种人口向按比例增加的老年人数量的转变，引发了人们对老龄化和与年龄相关的疾病的影响及其与认知能力下降的关系的担忧。影响个人的最常见的情况之一是 年龄是高血压，其发病率在美国所有成年人中为25%，在所有65岁以上的成年人中超过50%。目前，仅U S就有6000多万人患有这种疾病，估计其中一半可能得不到治疗。此外，越来越多的证据令人信服地表明，高血压除了衰老外，还会在多个领域产生认知功能障碍，即使是在血压轻度升高的情况下也是如此。 此外，高血压是脑血管痴呆症的主要危险因素，仅脑血管痴呆症就约占所有痴呆症的20%，并可能导致另外15%至20%的痴呆症病例。然而，高血压导致神经病变的机制尚不清楚，部分原因是研究这些过程的动物模型有限。本项目的目的是测试一种新型的诱发高血压的装置。 非人灵长类动物。该装置通过外科手术植入胸廓周围的猴子胸腔内。该装置可以在外部调节，以缩小动脉的直径(但不能完全收缩)，导致上肢和头部的血流量增加和高血压。通过在一段时间内逐渐调整设备，血压可以逐渐升高，直到引发高血压。我们将在五只猴子身上测试这种设备在不存活和短期存活的情况下。他们将被持续监测血压、身体状况 使用无线电遥测设备和数值比较植入前和植入后的温度、心电图和活动度。最后，作为了解在大脑中诱导神经病理过程的机制的初步努力的一部分，我们将调查大脑和主动脉的病理迹象。