Circulation Research. 2004;94:1083-1090
Published online before print March 11, 2004, doi: 10.1161/01.RES.0000125629.72053.95
Published online before print March 11, 2004, doi: 10.1161/01.RES.0000125629.72053.95
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© 2004 American Heart Association, Inc.
Cellular Biology |
Role of Calcium Cycling Versus Restitution in the Mechanism of Repolarization Alternans
From the Heart and Vascular Research Center and the Department of Biomedical Engineering, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio.
Correspondence to Kenneth R. Laurita, PhD, MetroHealth Campus, Case Western Reserve University, 2500 MetroHealth Dr, Rammelkamp, 6th Floor, Cleveland, OH 44109-1998. E-mail klaurita{at}metrohealth.org
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.
Key Words: electrophysiology • T-wave alternans • repolarization • Ca2+ cycling • optical mapping
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