β-Adrenergic Blockers as Antiarrhythmic and Antifibrillatory Compounds: An Overview

β-Adrenergic blockers have a wide spectrum of action for controlling cardiac arrhythmias that is larger than initially thought. Data from the past several decades indicate that, as an antiarrhythmic class, β-blockers remain among the very few pharmacologic agents that reduce the incidence of sudden cardiac death, prolong survival, and ameliorate symptoms caused by arrhythmias in patients with cardiac disease. As a class of compounds, 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 β-receptors. These individual compounds also differ in their selectivity for β1- and β2-receptors. Metoprolol is a β1-selective blocker, whereas carvedilol is a nonselective β1- and β2-blocker, an antioxidant, and has a propensity to inhibit α1-receptors and endothelin. Evolving data from controlled and uncontrolled 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-receptor blockers such as carvedilol and metoprolol extend beyond the ventricular tissue to encompass atrial cells and help maintain sinus rhythm in patients with atrial fibrillation, especially in combination with potent antifibrillatory agents such as amiodarone. This introduction provides a current perspective on these newer developments in the understanding of the antiarrhythmic and antifibrillatory actions of β-blockers.

Mechanism of negative chronotropic and inotropic effects of some antifibrillatory agents

Three compounds, 1,10-phenanthroline, tripyridine, and quinidine sulfate, which have potent antifibrillatory actions on isolated rabbit atria, were found to have negative chronotropic and inotropic effects on spontaneously beating rabbit atria. During the first 15–20 min, a progressive decrease in rate was observed with 1,10-phenanthroline and quinidine. A second period of rate decline was noted during which some of the atrial electrical complexes appeared to drop out. This second phenomenon was also noted with tripyridine. High amplification recording showed a splitting of the electrical complex with subsequent sudden losses of portions of the complex. Both tripyridine and quinidine produced apparent atrial standstill. During the standstill, amplification of the electrical recording showed regular electrical activity with the absence of contractions. It is concluded that quinidine and 1,10-phenanthroline affect the S-A node initially to produce atrial slowing; whereas, all three compounds produce a later atrial slowing by junctional blockade, presumably at anatomic junctions such as the region between the S-A node and the atrium, or at the intercalated discs within the atrium proper. The negative inotropic effects of all three compounds are in part explained by this junctional blockade.