Aging, Fitness & Failure: Diastolic Dysfunction

衰老、健身

• 批准号: 6758533
• 负责人: BENJAMIN D LEVINE
• 金额: $ 51.31万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6758533
• 关键词: aging; clinical research; congestive heart failure; coronary disorder; echocardiography; exercise; heart contraction; heart imaging /visualization /scanning; heart ventricle; human old age (65+); human subject; hypertension; magnetic resonance imaging; physical fitness; relaxation; rest; statistics /biometry; young adult human (21-34)

Aging is associated with alterations in left ventricular (LV) relaxation and compliance, even in the absence of manifest co-morbid conditions such as coronary artery disease or hypertension. This "diastolic dysfunction" may result in an elevation of LV filling pressure and cause signs and symptoms of congestive heart failure (CHF) despite the presence of preserved systolic function. This problem is critical for elderly CHF patients in whom nearly 1/2 may have predominantly diastolic dysfunction as the cause of their heart failure. The broad objective of this proposal is to determine the precise alterations of diastolic function associated with normal, healthy aging in humans, and compare these changes with those associated with CHF due to diastolic dysfunction. The hypotheses to be tested include: 1) Normal aging is associated with alterations in both relaxation and chamber compliance of the LV leading to impaired ventricular filling compared to healthy young adults. Moreover, such abnormalities will be substantially reduced in fit compared to sedentary healthy elderly subjects; 2) Patients with CHF and preserved LV systolic function have more pronounced abnormalities of LV chamber compliance and relaxation which contribute to the development of CHF; 3) Exercise training in both the healthy aged, as well as patients with CHF and diastolic dysfunction will improve abnormalities of diastolic function and will be an effective therapy for this disease. To test these hypotheses, we propose to accomplish the following specific aims: a) To measure the static component of diastole directly by constructing ventricular function (Starling) and LV pressure/volume curves in well, sedentary and fit elderly adults. The dynamic component of diastole will be assessed using state- of-the-art imaging techniques including: tissue Doppler imaging; color Doppler M-mode echo; and magnetic resonance imaging with myocardial tagging. b) To select a group of patients with CHF but preserved systolic function, and to quantify left ventricular relaxation and compliance using the same methods; c) To repeat the specific measures of diastolic function after a prolonged (one year) endurance exercise training program in both the sedentary elderly, and patients with CHF and diastolic dysfunction. These studies will result in a comprehensive understanding of the effect of normal aging and physical conditioning on LV diastolic function, and will identify the specific abnormalities of diastole which lead to CHF in the absence of contractile dysfunction. The precise dose of exercise necessary to restore normal diastolic function will be identified and will allow specific exercise prescription for these populations.

衰老与左心室（LV）松弛和依从性的改变有关，即使没有明显的合并症（例如冠状动脉疾病或高血压）。 尽管存在保留的收缩功能，但这种“舒张功能障碍”可能会导致LV充足压力的升高，并导致充血性心力衰竭（CHF）的体征和症状。 这个问题对于老年CHF患者至关重要，其中近1/2可能主要是舒张功能障碍是其心力衰竭的原因。 该提案的广泛目的是确定与人类正常，健康衰老有关的舒张功能的精确改变，并将这些变化与舒张功能障碍引起的与CHF相关的变化进行比较。 要测试的假设包括：1）正常衰老与LV的松弛和腔室依从性的改变有关，与健康的年轻人相比，左室的符合率会导致心室填充受损。此外，与久坐健康的老年受试者相比，这种异常将大大降低。 2）CHF和保留的LV收缩功能的患者的LV室依从性和放松的异常更为明显，这有助于CHF的发展； 3）在健康老龄化以及CHF和舒张功能障碍的患者中，运动训练都将改善舒张功能的异常，并将成为该疾病的有效疗法。 为了检验这些假设，我们建议实现以下特定目的：a）通过在井，久坐和拟合的老年人中构造心室功能（Starling）和LV压力/体积曲线直接测量舒张期的静态成分。舒张期的动态成分将使用现状的成像技术进行评估，包括：组织多普勒成像；颜色多普勒M模式回声;和磁共振成像具有心肌标记。 b）选择一组CHF但保留的收缩功能，并使用相同的方法量化左心室放松和依从性； c）在久坐的老年人和CHF和舒张功能障碍的患者中长时间（一年）耐力运动训练计划后，重复舒张功能的特定度量。 这些研究将使人们全面了解正常的衰老和物理条件对LV舒张功能的影响，并将确定舒张期的特定异常，这在没有收缩功能障碍的情况下导致CHF。 将确定恢复正常舒张功能所需的精确锻炼剂量，并允许对这些人群进行特定的运动处方。