Effect Of CaMK â…¡Inhibitor KN-93 On The Arrhythmias In Rabbit With Ventricular Hypertrophy

Objective: To investigate the effect of Ca2+/calmodulin-dependent protein kinaseⅡinhibitor KN-93 on the arrhythmias in rabbit with ventricular hypertrophy.Methods: Female rabbits were divided into 4 groups: Sham operation group, LVH group(left ventricular hypertrophy), KN-93 and KN-92 group. The LVH models were created by a partial constriction of the abdominal aorta in rabbits. Echocardiography was employed to measure the thickness of the walls of the ventricle before and after the operation. Transmembrane action potentials (TAP) from epicardium and endocardium were simultaneously recorded together with a transmural ECG by using arterially perfused rabbit ventricular wedge preparations. To observe the incidence of early afterdepolarization ( EAD )and torsade de pointes(Tdp) with slow stimulation , hypokalemic and hypomagnesaemic Tyrode's solution in left ventricular wedge preparations. The activity of CaMK activity were determined byγ-32P incorporation. Assay of CaM kinase activity of all groups was performed.Results: The induced rate of Tdp and activity of CaM in LVH group were higher than that of sham group( p<0.05). Increased activity of calmodulin kinase and the induced rate of Tdp in LVH were suppressed by KN-93. The inactive analog KN-92 does not have such effect.Conclusions: The KN-93 can suppress the activity of calmodulin kinase, which may be associated with therapeutic mechanism for antiarrhythmias.CaM kinaseⅡmay be an antiarrhythmic drug target.