beta(2)-Adrenoceptors and ventricular fibrillation

Abstract

beta-Adrenoceptor antagonists significantly reduce the incidence of sudden cardiac death in patients with contractile dysfunction. Contractile dysfunction is associated with a decline in beta(1)-adrenoceptors, no change in the number of beta(2)-adrenoceptors, and an increased responsiveness to beta(2)-adrenoceptor stimulation. Selective beta(2)-adrenoceptor blockade prevents ventricular fibrillation in a canine model of sudden cardiac death. Cardiac beta(2)-adrenoceptor stimulation increases L-type Ca(2+) currents, but unlike beta(1)-adrenoceptor stimulation, it fails to elicit phospholamban phosphorylation. Restoration of resting diastolic [Ca(2+)] following beta(2)-adrenoceptor-mediated increases in Ca(2+) influx is more dependent on Na(+)/Ca(2+) exchange, which generates an arrhythmogenic transient inward current that can trigger ventricular fibrillation.