Key result
In a guinea pig model, the mechanism underlying T-wave alternans was more closely associated with intracellular Ca2+ cycling rather than APD restitution, with comparable alternans thresholds.
In an intact heart model, the mechanism underlying T-wave alternans is more closely associated with intracellular Ca2+ cycling rather than APD restitution.
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Supports Ca2+ cycling as dominant mechanism for T-wave alternans in intact hearts; hypothesis-generating for human arrhythmia research.
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.
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Pruvot et al. (2004) studied T-wave alternans (n=7). High-resolution optical mapping and pacing was evaluated on Pacing rates (alternans threshold) at which T-wave, APD, and Ca2+ alternans first appeared. In a guinea pig model, the mechanism underlying T-wave alternans was more closely associated with intracellular Ca2+ cycling rather than APD restitution, with comparable alternans thresholds.
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