Cardiac adrenergic control and atrial fibrillation

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and it causes substantial mortality. The autonomic nervous system, and particularly the adrenergic/cholinergic balance, has a profound influence on the occurrence of AF. Adrenergic stimulation from catecholamines can cause AF in patients. In human atrium, catecholamines can affect each of the electrophysiological mechanisms of AF initiation and/or maintenance. Catecholamines may produce membrane potential oscillations characteristic of afterdepolarisations, by increasing Ca<sup>2+</sup> current, [Ca<sup>2+</sup>]<sub>i</sub> and consequent Na<sup>+</sup>–Ca<sup>2+</sup> exchange, and may also enhance automaticity. Catecholamines might affect reentry, by altering excitability or conduction, rather than action potential terminal repolarisation or refractory period. However, which arrhythmia mechanisms predominate is unclear, and likely depends on cardiac pathology and adrenergic tone. Heart failure (HF), a major cause of AF, causes adrenergic activation and adaptational changes, remodelling, of atrial electrophysiology, Ca<sup>2+</sup> homeostasis, and adrenergic responses. Chronic AF also remodels these, but differently to HF. Myocardial infarction and AF cause neural remodelling that also may promote AF. β-Adrenoceptor antagonists (β-blockers) are used in the treatment of AF, mainly to control the ventricular rate, by slowing atrioventricular conduction. β-Blockers also reduce the incidence of AF, particularly in HF or after cardiac surgery, when adrenergic tone is high. Furthermore, the chronic treatment of patients with β-blockers remodels the atria, with a potentially antiarrhythmic increase in the refractory period. Therefore, the suppression of AF by β-blocker treatment may involve an attenuation of arrhythmic activity that is caused by increased [Ca<sup>2+</sup>]<sub>i</sub>, coupled with effects of adaptation to the treatment. An improved understanding of the involvement of the adrenergic system and its control in basic mechanisms of AF under differing cardiac pathologies might lead to better treatments