Cardiac adrenergic control and atrial fibrillation

Dr. Workman, Antony. University of Glasgow Cardiovascular and Medical Sciences, 126 University Place, Glasgow, G12 8TA, Great Britain.

Atrial fibrillation (AF) is the most common cardiac arrhythmia. It causes substantial morbidity and mortality. Current pharmacological treatments are unsatisfactory. The autonomic nervous system, and particularly the sympathetic/parasympathetic balance, has a profound influence on the occurrence of AF. Adrenergic stimulation can affect, primarily via ß1-adrenoceptors, each of the atrial electrophysiological mechanisms involved in initiating and/or maintaining AF. ß1-stimulation may promote abnormal automaticity, by enhancing diastolic pacemaker ion currents. It may trigger afterdepolarisations, by increasing inward Ca2+ current, intracellular Ca2+ loading and Na+/Ca2+ exchange. It may also facilitate reentry, by increasing outward K+ current and shortening the action potential duration. However, which is the dominant mechanism in AF is unclear, and likely dependent on underlying cardiac pathology and sympathetic tone. Heart failure (HF), a major cause of AF, causes sympathetic activation and chronic adaptational changes, remodelling, of atrial electrophysiology, Ca2+ handling and ß-responses. Chronic AF itself also remodels these parameters, but differently to HF. Furthermore, myocardial infarction, and AF, cause atrial sympathetic hyperinnervation, neural remodelling, which may promote AF. The use of ß1-adrenoceptor antagonists is well established in the treatment of AF, mainly for controlling ventricular rate during AF, by slowing AV nodal conduction. ß1-blockers also reduce the incidence of AF in HF, and following cardiac surgery, when sympathetic tone is high. However, the chronic treatment of patients with ß1-blockers also remodels the atria; so called pharmacological remodelling, which features a potentially anti-arrhythmic prolongation of repolarisation and refractory period. An improved understanding of the involvement of the adrenergic system and its control in basic mechanisms of AF under differing cardiac pathologies may lead to better treatments for AF.