TREATMENT OF HEART FAILURE IN OLDER HUMANS

老年人心力衰竭的治疗

• 批准号: 2844521
• 金额: $ 12.26万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2844521
• 关键词: behavioral /social science research tag; beta adrenergic agent; beta adrenergic receptor; blood pressure; cardiovascular stress test; clinical trials; congestive heart failure; dosage; electrocardiography; functional ability; heart contraction; heart disorder chemotherapy; heart pharmacology; heart rate; human old age (65+); human subject; human therapy evaluation; isoproterenol; myocardium; neurotransmitter metabolism; norepinephrine; outcomes research; oxygen consumption; physical fitness; prognosis; quality of life; sympathetic nervous system

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.

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.