Abstract
ObjectivesThe 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.ResultsISO 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 MethodsPressure-overload cardiac hypertrophy was induced in mice by thoracic aortic banding. Arrhythmias were recorded by electrocardiogram in conscious mice.ConclusionsCaMKII 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.
Highlights
Heart failure (HF) is featured with high mortality and morbidity and healthcare expenditures due to the ineffective therapy
Recent studies in animal models revealed that Ca2+/calmodulin dependent protein kinase II (CaMKII) is excessively activated in cardiac hypertrophy and that CaMKII overexpression can induce cardiac hypertrophy, progressive HF and lethal ventricular arrhythmias [4]
We investigated the effects of CaMKII inhibition on suppression of the ventricular arrhythmias in left ventricular hypertrophy (LVH) mice and explored the possible underlying mechanisms
Summary
Heart failure (HF) is featured with high mortality and morbidity and healthcare expenditures due to the ineffective therapy. Half of HF patients died of sudden cardiac death (SCD), of which ventricular arrhythmias are the most common cause [1]. HF is often a transition from cardiac hypertrophy, a process initiated as compensation to pressure-overload. Inhibition of CaMKII protects against structural heart disease and inhibits ventricular arrhythmias [5]. Persistent activation of β-adrenergic pathway, a known case in cardiac hypertrophy and failure, can activate CaMKII and enhance Ca2+ cycling, which may trigger ventricular arrhythmias. We developed a pressure-overload LVH mouse model and utilized the conscious electrocardiogram (ECG) to monitor the occurrence of ventricular arrhythmias in mice under ISO stimulation. We investigated the effects of CaMKII inhibition on suppression of the ventricular arrhythmias in LVH mice and explored the possible underlying mechanisms
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