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

// Ying Feng 1,* , Jun Cheng 1,* , Baozhu Wei 1 and Yanggan Wang 1,2 1 Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, China 2 The Medical Research Institute of Wuhan University, Wuhan, China * These authors have contributed equally to this work Correspondence to: Yanggan Wang, email: // Keywords : arrhythmia; CaMKII; cardiac hypertrophy; adrenergic stimulation; Pathology Section Received : August 04, 2016 Accepted : January 23, 2017 Published : February 04, 2017 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.