Arrhythmogenic Mechanisms in a Mouse Model of Catecholaminergic Polymorphic Ventricular Tachycardia

• DOI: 10.1161/circresaha.107.148064
• Publication Date: 2007-09-14T01:49:05Z
• Authors: Marina Cerrone; Sami F. Noujaim; Elena G. Tolkacheva; Arkadzi Talkachou; Ryan O’Connell; Omer Berenfeld; Justus Anumonwo; Sandeep V. Pandit; Karen Vikstrom; Carlo Napolitano; Silvia G. Priori; José Jalife
• Keywords: Purkinje fibers; Fibrillation

Catecholaminergic polymorphic ventricular tachycardia (VT) is a lethal familial disease characterized by bidirectional VT, and fibrillation. VT caused enhanced Ca 2+ release through defective ryanodine receptor (RyR2) channels. We used epicardial endocardial optical mapping, chemical subendocardial ablation with Lugol’s solution, patch clamping in knockin (RyR2/RyR2 R4496C ) mouse model to investigate the arrhythmogenic mechanisms catecholaminergic VT. In isolated hearts, spontaneous arrhythmias occurred 54% of 13 RyR2/RyR2 9% 11 wild-type ( P =0.03) littermates perfused isoproterenol; 66% 12 20% 10 hearts caffeine epinephrine showed =0.04). Epicardial mapping that monomorphic manifested as concentric breakthrough patterns, suggesting focal origin His–Purkinje networks either or both ventricles. Monomorphic was clearly unifocal, whereas bifocal. Polymorphic initially multifocal but eventually became reentrant degenerated into Endocardial confirmed Purkinje fiber arrhythmias. Chemical right cavity solution induced complete bundle branch block converted 4 anesthetized mice. Under current clamp, single cells from generated delayed afterdepolarization–induced triggered activity at lower frequencies level adrenergic stimulation than wild-type. Overall, data demonstrate system an important source