title: Role of calcium cycling versus restitution in the mechanism of repolarization alternans.
abstract: T-wave alternans, a powerful marker of arrhythmic events, results from alternation in action potential duration (APD). The underlying cellular mechanism of APD alternans is unknown but has been attributed to either intracellular calcium (Ca2+) cycling or membrane ionic currents, manifested by a steep slope of cellular APD restitution. To address these mechanisms, high-resolution optical mapping techniques were used to measure action potentials and Ca2+ transients simultaneously from hundreds of epicardial sites in the guinea pig model of pacing-induced T-wave alternans (n=7). The pacing rates (ie, alternans threshold) at which T-wave (369+/-11 bpm), APD (369+/-21 bpm), and Ca2+ (371+/-29 bpm) alternans first appeared were comparable. Importantly, the site of origin of APD alternans and Ca2+ alternans consistently occurred together near the base of the left ventricle, not where APD restitution was steepest. In addition, APD and Ca2+ alternans were remarkably similar both spatially and temporally during discordant alternans. In conclusion, the mechanism underlying T-wave alternans in the intact heart is more closely associated with intracellular Ca2+ cycling rather than APD restitution.
authors.affiliation: Heart and Vascular Research Center and the Department of Biomedical Engineering, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio 44109-1998, USA.
authors.forename: Etienne J
authors.initials: EJ
authors.lastname: Pruvot
authors.forename: Rodolphe P
authors.initials: RP
authors.lastname: Katra
authors.forename: David S
authors.initials: DS
authors.lastname: Rosenbaum
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Laurita
mesh_terms: D000200:Action Potentials; D000703:Analog-Digital Conversion; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D020013:Calcium Signaling / Q000502:physiology*; D002304:Cardiac Pacing, Artificial; D004562:Electrocardiography; D005260:Female; D005456:Fluorescent Dyes / Q000032:analysis; D006168:Guinea Pigs; D006329:Heart Conduction System / Q000503:physiopathology*; D006352:Heart Ventricles / Q000503:physiopathology; D007091:Image Processing, Computer-Assisted; D007700:Kinetics; D011726:Pyridinium Compounds / Q000032:analysis
chemical_list: D005456:Fluorescent Dyes; D011726:Pyridinium Compounds; C050019:1-(3-sulfonatopropyl)-4-(beta)(2-(di-n-butylamino)-6-naphthylvinyl)pyridinium betaine