Effect of Daily Exercise on Cardiac Autonomic Regulation

日常运动对心脏自主调节的影响

• 批准号: 6542877
• 负责人: GEORGE Edward BILLMAN
• 金额: $ 36.88万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6542877
• 关键词: aerobic exercise; atropine; autonomic nervous system; baroreflex; beta adrenergic receptor; cardiovascular disorder risk; dogs; echocardiography; fluorescence microscopy; heart function; heart pharmacology; myocardial infarction; neuroregulation; nonhuman therapy evaluation; physiologic stressor; ventricular fibrillation

DESCRIPTION (provided by applicant): Epidemiological data demonstrate that aerobic exercise training can dramatically reduce cardiac mortality even in patients with pre-existing cardiac disease. The mechanisms responsible for this cardio protection remain largely to be determined. It is probable that exercise-induced changes in cardiac autonomic regulation play a major role in the improved cardiac mortality. Cardiac autonomic balance is altered by cardiac disease and the patients with the greatest changes (i.e., decreased parasympathetic and/or increased sympathetic activity) are also at the greatest risk for sudden death presumably due to ventricular fibrillation (VF). Exercise training can increase parasympathetic and decrease sympathetic activity and could thereby reduce mortality. Therefore, the proposed studies will test the central hypothesis that exercise training augments parasympathetic and/or reduces cardiac sympathetic activity and thereby protects against VF. Specific Aim #1 will test the hypothesis that exercise training alters cardiac autonomic balance in animals susceptible and resistant to VF. Specifically, cardiac autonomic balance will be evaluated in animals either resistant or susceptible to VF before, during and after the completion of an exercise conditioning program (8-10 weeks of daily treadmill running). The autonomic response to two different physiological stressors, submaximal exercise and acute myocardial ischemia, will be evaluated. Cardiac autonomic balance will be evaluated by pharmacological tests (agonist dose response, effects of selective antagonists), baroreflex sensitivity, and time series analysis of R-R interval variability. Specific Aim #2 will test the hypothesis that the cardiac autonomic changes induced by exercise training are responsible for the protection noted for this intervention. The effects of parasympathetic activity will be evaluated with a cholinergic antagonist. Thus, if parasympathetic enhancement is responsible for the protection, then atropine should reinstate VF in the susceptible animals. Specific Aim #3 will test the hypothesis that exercise training can reverse the increased Beta-adrenoceptor responsiveness that we have shown to occur in dogs that become susceptible to VF following myocardial infarction. Ventricular contractile responses to Beta1- and Beta2-adrenoceptor stimulation will be examined in vivo by echocardiography and in vitro by single cell fluorescence microscopy/video edge detection.

描述（由申请人提供）：流行病学数据表明，有氧运动训练可以显着降低心脏病死亡率，即使是患有心脏病的患者也是如此。负责这种心脏保护的机制在很大程度上仍有待确定。运动引起的心脏自主调节变化很可能在降低心脏死亡率方面发挥着重要作用。心脏病会改变心脏自主平衡，变化最大（即副交感神经减少和/或交感神经活动增加）的患者也可能因心室颤动（VF）而面临猝死的最大风险。运动训练可以增加副交感神经并减少交感神经活动，从而降低死亡率。因此，拟议的研究将检验运动训练增强副交感神经和/或减少心脏交感神经活动从而预防心室颤动的中心假设。具体目标#1将检验运动训练改变易感和抵抗心室颤动的动物的心脏自主平衡的假设。具体而言，将在运动调节计划（每天在跑步机上跑步 8-10 周）之前、期间和之后对抵抗或易感心室颤动的动物进行心脏自主平衡评估。将评估对两种不同生理应激源（次最大运动和急性心肌缺血）的自主反应。心脏自主平衡将通过药理学测试（激动剂剂量反应、选择性拮抗剂的作用）、压力感受反射敏感性和 R-R 间隔变异性的时间序列分析来评估。具体目标#2将检验这样的假设：运动训练引起的心脏自主变化负责这种干预措施的保护。将用胆碱能拮抗剂评估副交感神经活动的影响。因此，如果副交感神经的增强负责保护作用，那么阿托品应该可以恢复易感动物的室颤。具体目标#3将检验这样的假设：运动训练可以逆转β-肾上腺素受体反应性的增加，我们已经证明这种情况发生在心肌梗塞后易患心室颤动的狗身上。将通过超声心动图检查体内对β1-和β2-肾上腺素受体刺激的心室收缩反应，并通过单细胞荧光显微镜/视频边缘检测进行体外检查。