title: Potassium channel blockade amplifies cardiac instability numerical studies of torsades de pointes.
abstract: Suppression of responses to premature stimulation has been the guiding principle in managing many cardiac arrhythmias. Recent clinical trails revealed that sodium channel blockade increased the incidence of re-entrant cardiac arrhythmias resulting in sudden cardiac death, although the physiologic mechanism remains uncertain. Potassium channel blockade offers an alternative mechanism for suppressing responses to premature stimuli. We have developed a simple model of a 2D sheet of excitable cells. We can initiate re-entrant activation with stimuli timed to occur within a period of vulnerability (VP). Reducing the Na conductance increases the VP while reducing the K conductance increases the collective instability of the array, and arrhythmias similar to torsades de pointes seen in patients subjected to K channel blocked can be readily initiated. Thus, while K channel blockade may suppress excitability by prolonging the action potential duration, it appears to simultaneously exhibit proarrhythmic properties that result in complex re-entrant arrhythmias.
authors.affiliation: Division of Biomedical Engineering, Indian Institute of Technology, Madras.
authors.forename: C F
authors.initials: CF
authors.lastname: Starmer
authors.forename: M R
authors.initials: MR
authors.lastname: Reddy
authors.forename: A
authors.initials: A
authors.lastname: Namasivayam
authors.forename: M
authors.initials: M
authors.lastname: Singh
mesh_terms: D000200:Action Potentials / Q000502:physiology; D001146:Arrhythmia, Sinus / Q000503:physiopathology*; D055592:Biophysical Phenomena; D001703:Biophysics; D016757:Death, Sudden, Cardiac / Q000209:etiology; D004562:Electrocardiography / Q000706:statistics & numerical data; D006801:Humans; D008875:Middle Aged; D008954:Models, Biological; D009206:Myocardium / Q000166:cytology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000502:physiology; D016171:Torsades de Pointes / Q000503:physiopathology*
chemical_list: D026902:Potassium Channel Blockers; D015221:Potassium Channels; D026941:Sodium Channel Blockers; D015222:Sodium Channels