Diastolic Intracellular Calcium-Membrane Voltage Coupling Gain and Postshock Arrhythmias

Abstract

Rationale : Recurrent ventricular arrhythmias after initial successful defibrillation are associated with poor clinical outcome. Objective : We tested the hypothesis that postshock arrhythmias occur because of spontaneous sarcoplasmic reticulum Ca release, delayed afterdepolarization (DAD), and triggered activity (TA) from tissues with high sensitivity of resting membrane voltage ( V m ) to elevated intracellular calcium (Ca i ) (high diastolic Ca i –voltage coupling gains). Methods and Results : We simultaneously mapped Ca i and V m on epicardial (n=14) or endocardial (n=14) surfaces of Langendorff-perfused rabbit ventricles. Spontaneous Ca i elevation (SCaE) was noted after defibrillation in 32% of ventricular tachycardia/ventricular fibrillation at baseline and in 81% during isoproterenol infusion (0.01 to 1 μmol/L). SCaE was reproducibly induced by rapid ventricular pacing and inhibited by 3 μmol/L of ryanodine. The SCaE amplitude and slope increased with increasing pacing rate, duration, and dose of isoproterenol. We found TAs originating from 6 of 14 endocardial surfaces but none from epicardial surfaces, despite similar amplitudes and slopes of SCaEs between epicardial and endocardial surfaces. This was because DADs were larger on endocardial surfaces as a result of higher diastolic Ca i –voltage coupling gain, compared to those of epicardial surfaces. Purkinje-like potentials preceded TAs in all hearts studied (n=7). I K1 suppression with CsCl (5 mmol/L, n=3), BaCl 2 (3 μmol/L, n=3), and low extracellular potassium (1 mmol/L, n=2) enhanced diastolic Ca i –voltage coupling gain and enabled epicardium to also generate TAs. Conclusions : Higher diastolic Ca i –voltage coupling gain is essential for genesis of TAs and may underlie postshock arrhythmias arising from Purkinje fibers. I K 1 is a major factor that determines the diastolic Ca i –voltage coupling gain.