The Role of the Autonomic Central Nervous System in Mediating and Modifying the Action of Cardiac Antiarrhythmic Drugsa

The autonomic nervous system, particularly the sympathetic nervous system, plays an important role in initiating or perpetuating cardiac arrhythmias in various animal models and presumably also in man. The parasympathetic and sympathetic nervous systems interact in a complex manner in regulating the electrophysiologic properties of cardiac tissues. To the extent that a given arrhythmia is influenced by autonomic tone, the alteration in autonomic tone produced by an antiarrhythmic drug will modify the effects of the antiarrhythmic drug. Several antiarrhythmic drugs that are known to have direct electrophysiologic effects on cardiac tissues also reduce efferent sympathetic nerve activity by acting in the CNS. This centrally mediated effect on sympathetic activity likely plays an important role in the antiarrhythmic effects of these drugs. Other antiarrhythmic drugs interact directly with autonomic receptors on cardiac tissues in addition to producing their direct electrophysiological effects. The electrophysiologic effects of such antiarrhythmic drugs that interact with autonomic receptors are qualitatively modified by the magnitude and nature of the prevailing autonomic tone. These interactions between the autonomic nervous system and antiarrhythmic drugs must be kept in mind when the mechanism of action of these drugs is considered.