PET DETECTION OF THE EFFECTS OF AGING ON THE HUMAN HEART

PET 检测衰老对人类心脏的影响

• 批准号: 2612539
• 负责人: Robert J. Gropler
• 金额: $ 51.39万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2612539
• 关键词: aerobiosis; aging; blood flow measurement; cardiac output; clinical research; echocardiography; exercise; fatty acid metabolism; gender difference; glucose metabolism; heart circulation; heart function; heart metabolism; heart pharmacology; human old age (65+); human subject; magnetic resonance imaging; mechanical stress; myocardium; oxygen consumption; positron emission tomography; rest; volunteer; young adult human (21-34)

In the United States, cardiovascular disease is a leading cause of death and disability among people 65 years of age or older. There is an age- related decline in myocardial mechanical function that in men, can be ameliorated by exercise training. The mechanisms responsible for the decrease in mechanical function are poorly understood. Results of studies in experimental models of aging suggest that abnormalities in myocardial perfusion and intermediary metabolism may contribute to the decline in mechanical function. However, whether these observations are applicable to human aging is unknown. Our hypothesis is that with aging there is a decline in myocardial perfusion reserve and oxygen consumption and a shift in myocardial intermediary metabolism to a greater reliance on glucose utilization to support overall oxidative metabolism which together impairs systolic function particularly when there is an increased demand in myocardial work. Furthermore, we hypothesize that endurance exercise training in aged men will improve myocardial perfusion reserve and intermediary metabolism which in turn will have salutary effects on myocardial mechanical function particularly when myocardial work is increased. We will provide or disprove this hypothesis by addressing the following specific aims: 1. To determine in humans, the impact of aging on myocardial perfusion and intermediary metabolism, at rest and during pharmacological stress, as they related to changes in mechanical function at rest, during exercise and during pharmacological stress: 2. To determine in aged humans, the impact of endurance exercise training on myocardial perfusion and intermediary metabolism, at rest and during pharmacological stress as they relate to changes in mechanical function (at rest, during exercise and during pharmacological stress) and whether the impact of exercise training is related to gender. This research will further our understanding of the effects of aging on myocardial perfusion and intermediary metabolism as they relate to myocardial mechanical function in humans. Demonstration that myocardial perfusion and intermediary metabolism can be modified by endurance exercise training with subsequent salutory effects on myocardial function will provide a therapeutic strategy designed to improve left ventricular function or at least slow the progression of left ventricular dysfunction that occurs with aging.

在美国，心血管疾病是死亡的主要原因 和65岁以上的人群中的残疾。有一个年龄 - 在男性中，心肌机械功能的相关下降可能是 通过运动训练改善。 负责的机制 机械功能的降低知之甚少。 结果 衰老实验模型中的研究表明异常 心肌灌注和中介代谢可能有助于 机械功能下降。 但是，这些观察是否是 适用于人类衰老是未知的。 我们的假设是随着衰老 心肌灌注储备和氧气下降 消费和心肌中介代谢转变为 更大的依赖葡萄糖利用来支持总体氧化 新陈代谢会损害收缩功能，特别是当 心肌工作的需求增加。 此外，我们 假设在老年男性中进行耐力运动训练将有所改善 心肌灌注储备和中介代谢 将对心肌机械功能产生有益的影响 特别是当心肌工作增加时。 我们将提供或 通过解决以下特定目的：1。 为了确定人类，衰老对心肌灌注的影响和 中间代谢，在药理学胁迫下， 它们与休息时机械功能的变化有关 在药理学压力期间：2。确定年龄的人类 耐力运动训练对心肌灌注和 中介代谢，在药理学应力下， 它们与机械功能的变化有关（在锻炼过程中休息时 在药理学压力期间）以及运动的影响是否 培训与性别有关。 这项研究将进一步理解衰老对的影响 与心肌灌注和中介代谢有关 人类的心肌机械功能。演示心肌 灌注和中介代谢可以通过耐力来改变 运动训练，随后对心肌产生有益的影响 功能将提供旨在改善左侧的治疗策略 心室功能或至少减慢左进展 衰老发生的心室功能障碍。