Objective: Ventricular tachycardia/fibrillation (VT/VF) can recur repeatedly after defibrillation (i.e. electrical storm). We tested the hypothesis that intracellular Ca2+ (Cai overload during VF and sensitivity of membrane voltage (Vm) to Cai (Cai-Vm coupling gain) is important for post-shock arrhythmias. Methods and Results: We simultaneously mapped Cai and Vm on epicardial (n=14) or endocardial (n=14) surfaces of Langendorff-perfused rabbit ventricles. Spontaneous Cai elevation (SCaE) was noted after defibrillation in 32% of VT/VF at baseline, 83% during isoproterenol infusion. SCaE was reproducibly induced by rapid ventricular pacing and inhibited by ryanodine. We found triggered activities (TAs) originating from 6 of 14 endocardial surfaces but none from epicardial surfaces, despite similar SCaEs between epicardial and endocardial surfaces. This was because delayed afterdepolarizations induced by SCaEs were larger on endocardial surfaces due to higher Cai-Vm coupling gain. Purkinje-like potentials preceded the TAs. /K1 suppression with CsCl or BaCl2 enhanced Cai-Vm coupling gain and enabled epicardium to also generate TAs. Further enhancement of Cai overload and Cai-Vm coupling gain by low [K+]o induced post-shock VTs and spontaneous VF recurrences leading to electrical storm. Conclusions: Cai-Vm coupling gain is important for the genesis of post-shock VT/VF and electrical storm. Purkinje fibers serve as arrhythmogenic substrate because of its higher Cai-Vm coupling gain. /K1 is a major determinant for Cai-Vm coupling gain.
All Science Journal Classification (ASJC) codes
- Cardiology and Cardiovascular Medicine