Background: Alternans of early phase and of duration of action potential (AP) critically affect dispersion of refractoriness through their influence on conduction and repolarization. We investigated the phase relationship between the two alternans and its effect on conduction. Methods and Results: Transmembrane potentials recorded from ventricles of eight swine and three canines during paced activation intervals of ≤300 ms were used to quantify alternans of maximum rate of depolarization (|dv/dt|max) and of action potential duration (APD). Incidence of APD alternans was 62 and 76% in swine and canines. Alternans of APD was frequently accompanied with alternans of |dv/dt|max. Of these, 4 and 26% were out of phase in swine and canines, i.e., low |dv/dt|max preceded long APD. Computer simulations show that out of phase alternans attenuate variation of wavelength and thus minimize formation of spatially discordant alternans. Conclusion: The spontaneous switching of phase relationship between alternans of depolarization and repolarization suggests that mechanisms underlying these alternans may operate independent of each other. The phase between these alternans can critically impact spatial dispersion of refractoriness and thus stability of conduction, with the in phase relation promoting transition from concord to discord while out of phase preventing formation of discord.
Electrical stability in the heart is affected by restitution of action potential duration (APD), i.e. dependence of APD on preceding diastolic interval (DI) and memory, i.e. dependence of an APD on previous activations. Heterogeneity in APD restitution has been recently demonstrated by a number of studies. In the present study we explored whether memory in restitution is also expressed heterogeneously. Transmembrane potentials were recorded from endocardial and epicardial sides of both ventricles using 15 farm pigs. Oscillatory changes in DIs with a period of 100 beats revealed hysteresis in restitution from which quantitative measures of memory were computed. Results showed that hysteresis loop thickness, overall tilt and areas were larger in the endocardium than the epicaridum, 24.5 msec vs 14.2msec, 0.36 vs 0.23 and 6866 msec2 vs 4122 msec2 (p < 0.05). Except for overall tilt, memory was not significantly different between the two ventricles. Memory has been hypothesized to increase stability, thus, our results suggest that in the endocardium a decrease in stability predicted by increased slope may be offset by an increase in memory. Memory may provide an explanation for why experimental observations of alternans have not been consistent with the stability predicted by heterogeneous restitution.
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