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

A.E. Pollard
Proceedings of the 25th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (IEEE Cat. No.03CH37439)  
Objective: 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. Methods: To study these relationships, we modified parameters in the Luo-Rudy dynamic membrane equations to reflect physiologic conditions associated with phase 1b arrhythmias. Superthreshold delayed afterdepolarizations (DADs) formed after pacing. Coupling
more » ... . Coupling contributions were then examined using: (i) a single phase 1b myocyte connected via a variable resistance to a single normal myocyte, and (ii) a multicellular fiber with a 1-cm segment of phase 1b myocytes connected to a 1-cm normal segment having resistance changes that were confined to the ischemic segment. Integration of ionic, capacitive and coupling currents during DAD initiation allowed charge quantification. Results: In cell pairs, phase 1b myocyte DADs were suppressed at resistances where normal myocyte pacing resulted in phase 1b myocyte excitation. Coupling charge requirements limited capacitive charging in the phase 1b myocyte, which occurred in combination with diastolic hyperpolarization that shifted transmembrane potential from threshold. In multicellular fiber 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. Conclusions: These findings support the clinical and experimental observation that intermediate uncoupling is an important contributor to phase 1b arrhythmogenesis.  This article is referred to in the Editorial by J.R. de cytosolic accumulation of Ca , Mg , H and lipid Groot ( pages 350 -352) in this issue. metabolites [9], and increased tissue resistance [10][11][12][13] develop. With regional ischemia, these changes are confined to the poorly perfused tissue that is electrically 1 . Introduction coupled to normal myocardium at the ischemic border [4] where injury currents flow between regions. Border zone Ventricular myocardium becomes arrhythmogenic dur-interactions are important to arrhythmias because the ing the phase 1b interval of ischemia [1, 2] . During this relationships between source charge generation and down-1 interval, extracellular potassium ([K ] ) accumulation [3-stream sink charge requirements modulate membrane e 5], hypoxia-induced adenosine triphosphate (ATP) deple-depolarization and repolarization, and they also dictate tion [6,7], intracellular and extracellular acidosis [7,8], success or failure of action potential propagation. Detailed theoretical models have provided insights into ischemic influences on local action potentials and on
doi:10.1109/iembs.2003.1279481 fatcat:6lm44dswyzgmhjlziduh7rpkvy