Abstract 11960: Abnormal Ca2+ Dynamics Underlies Triggered Activity in a Rabbit Model of Long QT Syndrome. Analysis of Subcellular Data From a Beating Heart
Background: Delayed afterdepolarizations (DADs) are caused by spontaneous release of Ca2+ from overloaded sarcoplasmic reticulum (SR), which propagate through myocytes as a Ca2+ waves. Increased cytoplasmic Ca2+ (Cai) then depolarizes cell membrane by augmenting the NCX current. The subcellular mechanism of early afterdepolarizations (EADs), which cause arrhythmia in long QT syndrome (LQTS), is disputed.
Methods: Rabbit model of LQTS, involving perfusion of slowly paced (50 bpm) female heart with solution containing dofetilide and low concentration of K+ and Mg2+, was used for optical mapping of Ca2+ transient (CaT) and action potential (AP) at high-resolution (100 x 100 pixels; 1.5 μm/pixel).
Results: Propagated intracellular Ca2+ waves developed during diastole in LQTS during regular rhythm and eventually caused DADs. Secondary systolic peaks of CaT underlying EADs occur synchronously within the cell. Other abnormalities of Ca2+ dynamics, such as multiple chaotic intracellular Ca2+ waves, were also observed. K201 (ryanodine receptor stabilizer; 1 μM/L) prevented CaT abnormalities and ventricular tachycardia.
Conclusion: Abnormal Cai dynamics in LQTS causes both EADs and DADs. The systolic secondary Cai elevation underlying EAD occurs synchronously within the cell. However, its response to K201 indicates that it is caused by abnormal Ca2+ release from SR rather than ICaL reactivation.
- © 2013 by American Heart Association, Inc.