Hysteresis in DI independent mechanisms in threshold for transition between 1:1 and 2:2 rhythms in pigs

Previous studies have shown hysteresis in transition from 1:1 to 2:2 rhythms in action potential durations (APD) during decreasing and increasing cycle length pacing. As cycle lengths were constant, when alternans of APD occurred, so did of preceding diastolic intervals (DIs), which engaged the restitution mechanism, i.e. dependence of APD on preceding DI, making it impossible to determine whether the hysteresis originates from the DI independent or dependent mechanism. By using pacing with explicit control of DI, in the present study we investigated whether hysteresis in activation threshold exists in DI independent mechanism of alternans of APD. Transmembrane potentials were recorded from the left ventricles of 6 farm pigs, and the state transition was obtained from two pacing protocols where DIs decreased and increased in steps of 10 msec between 50 and 20 msec with 30 (15) beats at each DI level. Results showed hysteresis: for the 30 (15) beats protocol, onset and termination of alternans occurred at 27 (33) and 47 (49) msec DIs; average alternans amplitude was 22 (13) and 26 (15) msec for decreasing and increasing DIs. Because constant DI pacing was used, restitution dependent effect was eliminated, therefore, observation of hysteresis in our results suggests that restitution independent mechanisms such as activation memory also contribute to the hysteresis in this state transition.