Diastolic Intracellular Calcium-Membrane Voltage Coupling Gain and Postshock Arrhythmias
- 5 February 2010
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation Research
- Vol. 106 (2), 399-408
- https://doi.org/10.1161/circresaha.109.211292
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 (Vm) to elevated intracellular calcium (Cai) (high diastolic Cai–voltage coupling gains). 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 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 Cai–voltage coupling gain, compared to those of epicardial surfaces. Purkinje-like potentials preceded TAs in all hearts studied (n=7). IK1 suppression with CsCl (5 mmol/L, n=3), BaCl2 (3 μmol/L, n=3), and low extracellular potassium (1 mmol/L, n=2) enhanced diastolic Cai–voltage coupling gain and enabled epicardium to also generate TAs. Conclusions: Higher diastolic Cai–voltage coupling gain is essential for genesis of TAs and may underlie postshock arrhythmias arising from Purkinje fibers. IK1 is a major factor that determines the diastolic Cai–voltage coupling gain.Keywords
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