Chatzidou et al. prospectively randomized 60 patients with implantable cardioverter-defibrillators (ICDs) and electrical storm (ES) in a 1:1, double-blind design to therapy with propranolol (40 mg orally every 6 h) versus metoprolol (50 mg orally every 6 h). Secondary causes for the index presentation were excluded and all subjects received amiodarone. The authors found that patients treated with propranolol had a shorter length of stay with significantly reduced arrhythmic burden and ICD discharges at 48 h. The results clearly indicate that propranolol is a better antiarrhythmic drug than metoprolol for acute treatment of ES in those patients who have already received amiodarone.
As to why propranolol (a nonselective β-blocker) is more effective than metoprolol (a selective β1-blocker), the authors pointed to the down-regulation of β1 and up-regulation of β2 receptors in heart failure β2 receptor activation induces hypokalemia, and increases QT interval and dispersion of repolarization in the ventricular myocardium . Na-K pump inhibition by even moderate hypokalemia plays a critical role in promoting early afterdepolarization (EAD)–mediated arrhythmias by inducing a positive feedback cycle, activating Ca/calmodulin-dependent protein kinase II and enhancing late
INa . Therefore, the β2-blocking effects of propranolol in heart failure could be antiarrhythmic by preventing epinephrine-induced hypokalemia.
INa . Therefore, the β2-blocking effects of propranolol in heart failure could be antiarrhythmic by preventing epinephrine-induced hypokalemia.
Could something else help explain the results of the study? Propranolol was first synthesized over a half century ago and helped win the Nobel Prize for Sir James Black . Because of the focus on its β-blocking effects, its other actions are often not appreciated. Propranolol (but not metoprolol) blocks both the peak and the late (persistent) INa, flattens the APD restitution curve, and decreases the number of activation fronts during VF . Reduced INa could also reduce Ca overload, which may reduce the IKAS thus helping to suppress recurrent VT or VF. However, INablock occurs at higher propranolol drug concentrations than are required for beta-adrenergic antagonist. Because propranolol plasma concentrations were not measured in the present study, whether INa blocking effects contributed to the results remains unclear.
Propranolol, the most lipophilic beta blocker, can easily cross the lipid cell and blood-brain barrier and may cause seizures in overdose cases. Sodium channel blocking beta blockers are said to possess “membrane stabilizing activity” which potentiates toxicity in overdose.
Propranolol, the most lipophilic beta blocker, can easily cross the lipid cell and blood-brain barrier and may cause seizures in overdose cases. Sodium channel blocking beta blockers are said to possess “membrane stabilizing activity” which potentiates toxicity in overdose.
Propranolol Versus Metoprolol for Treatment of Electrical Storm in Patients With Implantable Cardioverter-Defibrillator
