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: 6750172
• 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/6750172
• 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，即使在患有心脏疾病的患者中，有氧运动训练也可以大大降低心脏死亡率。负责这种有氧保护的机制仍然在很大程度上确定。运动引起的心脏自主神经调节的变化很可能在改善心脏死亡率中起主要作用。心脏疾病的心脏自主平衡改变了，并且发生变化最大的患者（即副交感神经和/或交感神经活动的降低）也处于猝死的最大风险，可能是由于心室纤颤（VF）。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，拟议的研究将检验一个中心假设，即运动训练增加副交感神经和/或减少心脏交感神经活动，从而防止VF。特定目标＃1将检验以下假设：运动训练会改变动物的心脏自主平衡，对VF的敏感和抗性。具体而言，在锻炼调节计划（每天运行8-10周）之前，期间和之后，将在动物抗性或容易受到VF的抗性或容易受到VF敏感的动物中评估心脏自主平衡。将评估对两种不同生理压力源的自主反应：次最大运动和急性心肌缺血。心脏自主平衡将通过药理学测试（激动剂剂量反应，选择性拮抗剂的影响），Roreflex敏感性以及R-R间隔变异性的时间序列分析来评估。具体目的＃2将检验以下假设：运动训练引起的心脏自主神经变化是为此干预所述的保护。副交感活性的影响将通过胆碱能拮抗剂进行评估。因此，如果副交感神经增强负责保护，则阿托品应在易感动物中恢复VF。具体目标＃3将检验以下假设：运动训练可以逆转我们已证明在心肌梗塞后容易受到VF的狗中发生的β-肾上腺素受体反应性的增加。将通过超声心动图和单细胞荧光显微镜/视频边缘检测来检查对BetA1-和beta2-肾上腺素受体刺激的心室收缩反应。