title: Effects of simulated potassium blockade on the dynamics of triggered cardiac activity.
abstract: Under certain conditions, drugs that partially block transmembrane potassium currents in ventricular myocytes predispose patients to ventricular tachyarrhythmias. Although the precise mechanisms by which potassium blockade initiates tachyarrhythmias are unknown, it is believed that early afterdepolarizations (EADs) may play a role. Using the Luo-Rudy kinetic model of the ventricular action potential, we examine the effect of potassium blockade on the likelihood of observing triggered cardiac activity in a system of two coupled kinetic patches. We found that (i) phase 2 EADs are capable of triggering full action potentials in neighboring tissue if the patches are separated by a relatively large resistive barrier, and (ii) partial potassium blockade can either increase or decrease triggering probabilities depending on coupling resistivity. To understand the dynamic contribution of potassium blockade to triggered activity, the two-patch model is decomposed into two single patches. In one of the patches we compute the stability properties of simulated EADs (arising from phase 2 of the ventricular action potential) as a function of potassium blockade. The EAD stability properties are then related to the frequency-amplitude response of the neighboring patch. From the analysis of the decomposed system we found (iii) that increases in triggering probabilities brought about by potassium blockade may result from frequency and amplitude shifts of stable EAD oscillations. The first finding suggests a mechanism by which potassium blockade could induce EAD-triggered arrhythmias within the setting of chronic myocardial infarction. The second and third findings may partially explain why potassium blockade is antiarrhythmic in some patients, and proarrhythmic in others.
authors.affiliation: Cardiovascular Research Institute, University of California, San Francisco 94143.
authors.forename: W J
authors.initials: WJ
authors.lastname: Gibb
authors.forename: M B
authors.initials: MB
authors.lastname: Wagner
authors.forename: M D
authors.initials: MD
authors.lastname: Lesh
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D003198:Computer Simulation; D006321:Heart / Q000502:physiology*; D006801:Humans; D008955:Models, Cardiovascular; D009203:Myocardial Infarction / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects*; D017180:Tachycardia, Ventricular / Q000209:etiology* / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D015221:Potassium Channels; D014665:Vasodilator Agents