Abstract 19050: Inhibition of CaMKII blocks Inducible Ventricular Tachycardia/Fibrillation and Triggered Activity in a Canine Model of Myocardial Ischemia

Introduction: Ventricular tachycardia or fibrillation (VT/VF) of focal origin due to triggered activity (TA) from delayed afterdepolarizations is reproducibly inducible after anterior coronary artery occlusion in the dog. Calcium/Calmodulin Dependent Protein Kinase II (CaMKII) has been implicated in arrhythmias in small animal models. Here, we investigated the effect of inhibition of CaMKII on inducible VT/VF in our model. Methods: 25 chloralose anesthetized dogs received either an inhibitor of CaMKII, KN-93 at 2 mcg/kg IV, or saline for time controls. Endocardium from ischemic sites (3-D mapping utilizing customized Matlab 7.11 software) was sampled for oxidized CaMKII or studied in vitro with standard microelectrode techniques. Results (mean ± SE, *=p Conclusion: In ischemic VT/VF, KN-93 specifically blocked all inducible focal VT/VF due to TA without evidence of conduction or refractory period change in our large animal model of ischemia.