Modulation of triggered activity by uncoupling in the ischemic border. A model study with phase 1b-like conditions

Triggered beats during regional ischemia may depend upon the electrical source and sink charge interactions between adjacent regions of normal and ischemic cardiac tissue that are partly controlled by electrical coupling. To study these relationships, we modeled parameters in the Luo-Rudy dynamic membrane equations to represent physiologic conditions associated with phase 1b arrhythmias. Superthreshold delayed after depolarizations (DADs) formed after pacing. Coupling contributions were then examined using a multicellular ber with a 1 cm segment of phase 1b myocytes connected to a 1 cm normal segment having resistance changes that were conned to the ischemic segment. In multicellular ber simulations, DADs were suppressed with strong coupling in the phase 1b segment. Moderate uncoupling of that segment allowed superthreshold DAD formation away from the border that initiated action potential propagation in the normal segment. With severe uncoupling, propagation failed at the border. These findings support the clinical and experimental observation that intermediate coupling is an important contributor to phase 1b arrhythmogenesis.