Calcium cycling as mechanism of repolarization alternans onset in the intact heart
Etienne Pruvot
Authors: Kenneth R Laurita; David S Rosenbaum; Rodolphe P Katra; Etienne Pruvot
8:00 - 6:00

T-wave alternans (T-ALT), a powerful marker of arrhythmic events, results from alternation in cellular repolarization. The underlying cellular mechanism is unknown, but has been attributed to either: 1. membrane ionic currents, manifested by steep slope of action potential duration (APD) restitution in cells exhibiting ALT, or 2. intracellular calcium (Ca) cycling. High resolution optical mapping techniques were used to measure action potentials and Ca transients simultaneously from 128 epicardial sites in the guinea pig model of pacing induced T-ALT (n=5). ALT of APD (APD-ALT) and Ca amplitude (Ca-ALT) were measured over a broad range of cycle lengths (CL). The CL (i.e. ALT threshold) at which T-ALT (162?4 ms), APD-ALT (160?0 ms), and Ca-ALT (156?5 ms) first appeared were similar (p=ns). Likewise, the site of origin of APD-ALT and Ca-ALT was nearly identical in all experiments and always occurred near the base of the left ventricle. However, the site of Ca-ALT and APD-ALT onset was not located where APD restitution was steepest. Conclusion: The onset of APD-ALT was closely related to Ca-ALT but not APD restitution, suggesting that the mechanism underlying the initiation of T-ALT is more closely associated with intracellular Ca cycling rather than membrane repolarization currents.