Antiarrhythmic mechanisms of beta blocker therapy

Sympathetic activity plays an important role in modulation of cardiac rhythm. Indeed, while exerting positive tropic effects in response to physiologic and pathologic stressors, beta-adrenergic stimulation influences cardiac electrophysiology and can lead to disturbances of the heart rhythm and potentially lethal arrhyttunias, particularly in pathological settings. For this reason, beta-blockers are widely utilized clinically as antiarrhythmics. In this review, the molecular mechanisms of beta-adrenergic action in the heart, the cellular and tissue level cardiac responses to beta-adrenergic stimulation, and the clinical use of beta-blockers as antiarrhythmic agents are reviewed. We emphasize the complex interaction between cardiomyocyte signaling, contraction, and electrophysiology occurring over multiple time- and spatial-scales during pathophysiological responses to beta-adrenergic stimulation. An integrated understanding of this complex system is essential for optimizing therapies aimed at preventing arrhydunias.