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(Circulation. 2008;118:17-25.)
© 2008 American Heart Association, Inc.

Arrhythmia/Electrophysiology

Role of Conduction Velocity Restitution and Short-Term Memory in the Development of Action Potential Duration Alternans in Isolated Rabbit Hearts

Sergey Mironov, PhD; José Jalife, MD; Elena G. Tolkacheva, PhD

From the Department of Pharmacology, Institute for Cardiovascular Research, SUNY Upstate Medical University, Syracuse, NY.

Correspondence to Elena Tolkacheva, SUNY Upstate Medical University, Department of Pharmacology, Institute for Cardiovascular Research, 750 E Adams St, Syracuse, NY, 13210. E-mail talkacal{at}upstate.edu

Received August 28, 2007; accepted April 24, 2008.

Background— Spatially discordant alternans (SDA) has been linked to life-threatening arrhythmias. The mechanisms underlying SDA development in cardiac tissue remain unclear.

Methods and Results— We investigated the role of conduction velocity (CV) restitution and short-term memory in the organization and evolution of alternans in action potential duration using high-resolution optical mapping of the epicardial surface in 8 isolated, Langendorff-perfused rabbit hearts. To assess the spatial organization of alternans, we tracked the evolution of nodal lines that separate out-of-phase regions of SDA. We measured the action potential duration heterogeneity index and maximal slope of CV restitution and estimated the effects of short-term memory by calculating time constant of action potential duration accommodation (). We found that 2 mechanisms underlie the development of SDA in the heart, leading to 2 distinct behaviors of nodal lines. The first mechanism is based on steep CV restitution and is associated with small and stable nodal lines. The second mechanism is associated with short-term memory (large ) and is characterized by shallow CV restitution and unstable behavior of nodal lines. The maximum slope of the CV restitution was steeper (18.16±3.34 m/s²) and was smaller (=4.31±0.33 stimuli) for areas with stable nodal lines than for areas with unstable nodal lines (6.32±0.96 m/s² and =10.3±1.84 stimuli; P<0.01).

Conclusions— Our results provide new insight into the mechanisms underlying SDA formation in the rabbit heart. Specifically, our results suggest that a new mechanism associated with short-term memory underlies SDA formation in the heart, in addition to steep CV restitution.

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Clinical Summaries
Circulation 2008 118: 1-2. [Full Text]