TREATMENT OF HEART FAILURE IN OLDER HUMANS

这项提案将确定医疗干预的程度， 使用β-肾上腺素能受体拮抗剂治疗，将增强 老年充血性心力衰竭患者的功能独立性 (瑞士法郎)。此外，这种干预改变交感神经的效果 神经系统(SNS)功能将作为病理生理检查 可能有助于治疗反应的机制。首字母 这项干预发展研究的步骤将是定义 该人群SNS功能的生理特征 心肌收缩功能正常的老年人。第一 有待检验的假设是，与年龄较大的人相比， 心肌收缩功能，心肌受损的老年人 收缩能力在SNS活性上有不成比例的增加 比较它们在β-肾上腺素能受体反应性方面的降低。 与这一假设有关的两个具体目标：具体目标1： 表征SNS功能，系统SNS活动水平(SNSA) ~(3/H)去甲肾上腺素动力学与心脏和心脏的隔室分析 正常老年人的外周β-肾上腺素能受体功能 和受损的心肌收缩能力。具体目标2：确定 心肌收缩功能障碍与SNS功能的关系 (例如SNSA水平和β-肾上腺素能受体反应性)， 残疾的功能测量(例如，VO/2max和跑步机运动 耐受性)，以及老年人的生活质量。 要在提案的干预部分进行检验的假设 是β-肾上腺素能拮抗剂治疗抑制SNS的程度 活动度可以预测心肌收缩功能改善的程度 残疾和生活质量的反应性和功能测量 在心肌收缩功能受损的老年患者中。相关的 具体目标规定：具体目标3：确定贝塔的影响-- 拮抗剂治疗对心肌收缩功能、SNS活性(SNSA)、β-氨基丁酸的影响 受体反应性、残疾的功能测量和质量 患有心肌功能障碍的老年人的生活。 这项提案中概述的研究将确定Beta- 肾上腺素能拮抗剂治疗对体能、功能的影响 以及老年充血性心力衰竭患者的生活质量。此外， 对治疗有反应的病理生理学 关于SNS功能在调节心肌收缩性能中的作用 也将被确定。

This proposal will identify the extent to which a medical intervention, therapy with a beta-adrenergic receptor antagonist, will enhance the functional independence of older humans with congestive heart failure (CHF). In addition, the effect of this intervention to modify sympathetic nervous system (SNS) function will be tested as a pathophysiologic mechanism which may contribute to the response to treatment. The initial step in this intervention development study will be to define the range of physiologic characteristics of SNS function in this population relative to older humans with normal myocardial systolic function. The first hypothesis to be tested is that compared to older humans with normal myocardial contractility, older humans with impaired myocardial contractility have a disproportionate increase in SNS activity in comparison to their reduction in beta-adrenergic receptor responsiveness. Two specific aims pertain to this hypothesis: Specific Aim 1: To characterize SNS function, the level of systemic SNS activity (SNSa) using compartmental analysis of 3/H-norepinephrine kinetics and cardiac and peripheral beta-adrenergic receptor function, in older humans with normal and impaired myocardial contractility. Specific Aim 2: To determine the association between myocardial contractile dysfunction and SNS function (e.g. level of SNSa and beta-adrenergic receptor responsiveness), functional measures of disability (e.g. VO/2max and treadmill exercise tolerance), and quality of life in older humans. The hypothesis to be tested in the intervention component of the proposal is the degree to which beta-adrenergic antagonist therapy suppresses SNS activity will predict the extent of improvements in myocardial contractile responsiveness and functional measures of disability and quality of life among older patients with impaired myocardial contractility. The related specific aim states: Specific Aim 3: To determine the effects of beta- antagonist therapy on myocardial contractility, SNS activity (SNSa), beta- receptor responsiveness, functional measures of disability and quality of life in older humans with myocardial dysfunction. The studies outlined in this proposal will determine the effect of beta- adrenergic antagonist therapy on physical performance, functional ability and quality of life in older humans with CHF. In addition, the pathophysiology which contributes to the response to treatment with respect to the role of SNS function in regulating myocardial contractility will also be determined.