CaMKII inhibition reduces isoproterenol-induced ischemia and arrhythmias in hypertrophic mice.

Abstract

OBJECTIVES: The Ca/calmodulin-dependent protein kinase II (CaMKII), an arrhythmogenic molecule, is excessively activated in cardiac hypertrophy. Here, we investigated the effect of CaMKII inhibition in isoproterenol (ISO)-induced arrhythmias in hypertrophic mice. RESULTS: ISO induced multiple types of arrhythmias in the hypertrophic mice but not in the normal mice. The QTc intervals were prolonged and the amplitudes of T waves were increased significantly by ISO prior to arrhythmia initiation. Inhibition of CaMKII prevented ISO-induced QTc prolongation and T wave elevation and abrogated arrhythmia induction. MATERIALS AND METHODS: Pressure-overload cardiac hypertrophy was induced in mice by thoracic aortic banding. Arrhythmias were recorded by electrocardiogram in conscious mice. CONCLUSIONS: CaMKII inhibition is effective in suppressing adrenergic activation-induced ventricular arrhythmias in cardiac hypertrophy, of which the ventricular ischemia-induced CaMKII activation plays an important role.