Published Online
on June 16, 2008

A more recent version of this article appeared on July 1, 2008

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Submitted on August 28, 2007
Accepted on April 24, 2008

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, and Elena G. Tolkacheva PhD^*

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

^* To whom correspondence should be addressed. E-mail: talkacal{at}upstate.edu.

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.

Key words: action potentials • alternans • mapping • memory • restitution

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