AUTONOMIC MODULATION OF RESTING AND EXERCISE CARDIAC PERFORMANCE

静息和运动时心脏功能的自主调节

• 批准号: 3745459
• 负责人: E LAKATTA
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 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/3745459
• 关键词: aerobic exercise; aging; beta adrenergic agent; beta antiadrenergic agent; blood pressure; electrocardiography; female; gender difference; heart circulation; heart contraction; heart imaging /visualization /scanning; heart pharmacology; heart rate; heart ventricle; human middle age (35-64); human old age (65+); human subject; intracardiac volume; male; physiologic stressor; propranolol; thallium; young adult human (21-34)

Advancing age is accompanied by profound changes in autonomic nervous syste activity, both at rest and during exercise as well as reduction in the cardiovascular response to autonomic stimulation. We have undertaken three separate but conceptually interrelated studies to quantify the relationship between aging and autonomic modulation of cardiovascular performance. A. Efferent muscle sympathetic nerve activity (MSNA) recording from the peroneal nerve will be performed in the Baltimore Longitudinal Study of Aging (BLSA) men and women across a broad age range at rest and in response to baroreflex stimulation and static exercise. We hypothesize that in addition to age, other factors such as gender, aerobic fitness and body composition will modulate the MSNA response to these stimuli. B. To ascertain the importance of the beta-adrenergic system on age-associated changes in hemodynamics during aerobic exercise (EX), we performed maximal cycle EX in 25 healthy men ages 28-72 yr from the BLSA after acute beta- blockade with intravenous propranolol. In these men,end-diastolic volume index (EDVI) at peak workload declined with age (r= - 0.45) causing an age- associated decline in stroke volume index (SVI) (r= 0.48, p<0.05) not present in 70 unblocked men. The decline in heart rate (HR) with age in propranolol-treated men was blunted (0.46 beats/min/yr) compared to control (1.09 beats/min/yr). The primary reason for the slope shifts in the age regressions after propranolol was a large increase in EDVI and SVI and a large decrease in HR in younger men. Similarly, intravenous propranolol resulted in reduced peak filling rates with EX in young (27 q 8 yr) but not older (62 q 6 yr) men relative to their unmedicated age peers. We conclude that age differences in beta-adrenergic responsiveness underlie many of the age-associated changes in hemodynamics during vigorous aerobic EX. C. To determine the role of the autonomic nervous system on age-associated differences in aerobic capacity and plasma catecholamines, we performed acute autonomic blockade with intravenous propranolol (0.15 mg/kg) and atropine (0.025 mg/kg) in 10 young (<40 yr old) and 10 older (>60 yr old) healthy BLSA volunteers prior to maximal treadmill exercise, in a placebo- controlled crossover trial. Plasma catecholamines were monitored before, during and immediately following exercise. Statistical analysis will determine whether age per se differentially modifies the effect of autonomi blockade on VO2max, HR and blood pressure response and plasma catecholamine during maximal exercise.

增龄伴随着自主神经系统的深刻变化 在休息和锻炼期间的活动，以及减少 心血管对自主神经刺激的反应。我们已经承担了三项任务 独立但在概念上相互关联的研究，以量化关系 衰老和心血管功能的自主调节之间的关系。一个。 传出肌交感神经活动(MSNA)的记录 将在巴尔的摩纵向研究中进行腓神经手术 不同年龄段的男性和女性在休息和反应时的老龄化(BLSA) 压力感受性反射刺激和静态运动。我们假设在 除年龄外，性别、有氧健身和身体状况等其他因素 成分将调节MSNA对这些刺激的反应。B.到 确定β-肾上腺素能系统在年龄相关性疾病中的重要性 有氧运动期间血流动力学的变化(EX)，我们进行了最大 25名来自BLSA的28-72岁健康男性在急性贝塔试验后进行周期锻炼 静脉注射心得安进行阻断。在这些人中，舒张末容量 峰值负荷指数(EDVI)随年龄增长而下降(r=-0.45)，导致年龄- 每搏输出量指数(SVI)的相关下降(r=0.48，p&lt；0.05) 有70名畅通无阻的男性。心率(HR)随着年龄的增长而下降 与对照组相比，心得安治疗组的男性钝化(0.46次/分钟/年) (1.09次/分钟/年)。坡度随年龄变化的主要原因 心得安治疗后EDVI和SVI显著增加， 年轻男性的心率大幅下降。同样，静脉注射心得安 导致杨氏(27季度8年)的EX峰值填充率降低，但不是 与未服药的同龄人相比，年龄较大的男性(62岁，6岁)。我们得出结论 β-肾上腺素能反应性的年龄差异是许多 剧烈有氧运动中血流动力学的年龄相关变化。C.至 确定自主神经系统在年龄相关疾病中的作用 有氧能力和血浆儿茶酚胺的差异，我们进行了 普奈洛尔(0.15 mg/kg)静脉注射急性自主神经阻滞 阿托品(0.025 mg/kg)用于10名年轻人(40岁)和10名老年人(60岁) 健康的BLSA志愿者在最大限度的跑步机运动前，服用安慰剂- 对照交叉试验。血浆儿茶酚胺以前被监测过， 在运动期间和之后立即运动。统计分析将 确定年龄本身是否会不同地改变自主性的影响 阻断最大摄氧量、心率和血压反应及血浆儿茶酚胺 在最大限度的运动期间。