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，心血管疾病是导致死亡的主要原因 65 岁或以上人群的残疾。有一个年龄—— 男性心肌机械功能的相关下降可能是 通过运动训练可以改善。 负责的机制 人们对机械功能下降知之甚少。 结果 衰老实验模型的研究表明， 心肌灌注和中间代谢可能有助于 机械功能下降。 然而，这些观察结果是否 适用于人类衰老尚不清楚。 我们的假设是随着年龄的增长 心肌灌注储备和氧气下降 消耗和心肌中间代谢的转变 更多地依赖葡萄糖利用来支持整体氧化 新陈代谢共同损害收缩功能，特别是当 心肌工作的需求增加。 此外，我们 假设老年男性的耐力运动训练会有所改善 心肌灌注储备和中间代谢，进而 对心肌机械功能有有益作用 特别是当心肌做功增加时。 我们将提供或 通过解决以下具体目标来反驳这一假设：1. 确定人类衰老对心肌灌注和 休息时和药理应激期间的中间代谢，如 它们与休息时和运动期间机械功能的变化有关 以及在药物应激期间： 2. 为了确定老年人中， 耐力运动训练对心肌灌注的影响 休息时和药理应激期间的中间代谢 它们与机械功能的变化有关（休息时、运动时 以及药物应激期间）以及运动的影响是否 培训与性别有关。 这项研究将进一步加深我们对衰老影响的理解 心肌灌注和中间代谢，因为它们与 人类心肌机械功能。证明心肌 灌注和中间代谢可以通过耐力来改变 运动训练对心肌产生随后的有益作用 功能将提供旨在改善左侧的治疗策略 心室功能或至少减缓左心室的进展 随着年龄的增长而发生的心室功能障碍。