Cardiac autonomic neural remodeling and susceptibility to sudden cardiac death: effect of endurance exercise training.
Sudden cardiac death resulting from ventricular tachyarrhythmias remains the leading cause of death in industrially developed countries, accounting for between 300,000 and 500,000 deaths each year in the United States. Yet, despite the enormity of this problem, both the identification of factors contributing to ventricular fibrillation as well as the development of safe and effective antiarrhythmic agents remain elusive. Subnormal cardiac parasympathetic regulation coupled with an elevated cardiac sympathetic activation may allow for the formation of malignant ventricular arrhythmias. In particular, myocardial infarction can reduce cardiac parasympathetic regulation and alter beta-adrenoceptor subtype expression enhancing beta(2)-adrenoceptor sensitivity that can lead to intracellular calcium dysregulation and arrhythmias. As such, myocardial infarction can induce a remodeling of cardiac autonomic regulation that may be required to maintain cardiac pump function. If alterations in cardiac autonomic regulation play an important role in the genesis of life-threatening arrhythmias, then one would predict that interventions designed to either augment parasympathetic activity and/or reduce cardiac adrenergic activity would also protect against ventricular fibrillation. Recently, studies using a canine model of sudden death demonstrate that endurance exercise training (treadmill running) enhanced cardiac parasympathetic regulation (increased heart rate variability), restored a more normal beta-adrenoceptor balance (i.e., reduced beta(2)-adrenoceptor sensitivity and expression), and protected against ventricular fibrillation induced by acute myocardial ischemia. Thus exercise training may reverse the autonomic neural remodeling induced by myocardial infarction and thereby enhance the electrical stability of the heart in individuals shown to be at an increased risk for sudden cardiac death.
Billman
George E
GE
Dept of Physiology and Cell Biology, The Ohio State Univ, Columbus, OH 43210-1218, USA. billman.1@osu.edu
D000818:Animals; D001341:Autonomic Nervous System / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism; D016757:Death, Sudden, Cardiac / Q000209:etiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004285:Dogs; D005081:Exercise Therapy; D006321:Heart / Q000294:innervation*; D006339:Heart Rate; D006801:Humans; D009203:Myocardial Infarction / Q000150:complications / Q000378:metabolism / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000378:metabolism; D010807:Physical Endurance; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D012307:Risk Factors; D017180:Tachycardia, Ventricular / Q000209:etiology / Q000378:metabolism / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*
D018343:Receptors, Adrenergic, beta-2; D002118:Calcium