Impact of beta blockades in the treatment of arrhythmias: from bench to bedside

Activation and application of β-adrenergic pathways/agonists in the heart is the most powerful endogenous way to increase the mechanical performance of cardiac tissues to meet the requirements of a fight-or-flight situation or stress. On the other hand, sustained activation of cardiac β-receptors initiates maladaptive remodeling of the myocardium leading to cardiomyopathies and heart failure. Because both acute and chronic stimulation of β-adrenoceptors are arrhythmogenic, the application of β-receptor blockers exerts effective antiarrhytmic actions at both short and long time scale. As a class of antiarrhythmics, β -blockers have a fundamental pharmacologic property that attenuates the effects of competitive adrenergic receptors. However, the net clinical effects of the different β-receptor blockers may vary quantitatively because of variations in associated intrinsic sympathomimetic agonism and in their intrinsic potency for binding to beta-receptors. These individual drugs also differ in their selectivity for β1, β2 and β3-receptors; some β-blockers are β1-selective blockers, and others are nonselective β1/β2/β3-blockers. Evolving data from clinical trials suggest that there are clinically significant differences among this class of drugs. Recent evidence also suggests that the antiarrhythmic actions of certain β blockers extend beyond the ventricular tissue to encompass atrial cells and help maintain sinus rhythm in patients with atrial fibrillation. Physiological, and pharmacological properties of the β-adrenoceptor related signaling, the role of β receptor subtypes, consequences of acute and long term β-adrenergic stimulation and the underlying proarrhythmic mechanisms, including the changes in cardiac ion currents and Ca²⁺ handling, are discussed in this symposium together with the clinical relevance of cardioprotective β-blocking therapy.