Effect of Daily Exercise on Cardiac Autonomic Regulation

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著降低心脏病死亡率，即使在既存心脏病患者中也是如此。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神经调节的改变可能在心脏死亡率的降低中起主要作用。心脏自主平衡被心脏疾病改变，并且具有最大变化的患者（即，副交感神经活动减少和/或交感神经活动增加）也是猝死的最大风险，推测是由于心室纤维性颤动（VF）。运动训练可以增加副交感神经和减少交感神经活动，从而降低死亡率。因此，拟议的研究将测试中心假设，即运动训练增强副交感神经和/或减少心脏交感神经活动，从而防止VF。具体目标#1将检验运动训练改变VF易感和耐受动物心脏自主神经平衡的假设。具体而言，在运动调节计划（8-10周的每日跑步机跑步）完成之前、期间和之后，将在抗VF或易受VF影响的动物中评价心脏自主平衡。将评价对两种不同生理应激源（亚极量运动和急性心肌缺血）的自主神经反应。将通过药理学试验（激动剂剂量反应、选择性拮抗剂的作用）、压力反射敏感性和R-R间期变异性的时间序列分析评价心脏自主神经平衡。具体目标#2将检验运动训练诱导的心脏自主神经变化是该干预措施保护作用的原因这一假设。将使用胆碱能拮抗剂评价副交感神经活性的影响。因此，如果副交感神经增强是保护的原因，那么阿托品应该恢复敏感动物的VF。具体目标#3将检验运动训练可以逆转我们已经证明在心肌梗死后对VF易感的犬中发生的β-肾上腺素受体反应性增加的假设。将通过超声心动图在体内和通过单细胞荧光显微镜/视频边缘检测在体外检查对β 1和β 2肾上腺素受体刺激的心室收缩反应。

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.