title: Off-site control of repolarization alternans in cardiac fibers.
abstract: Repolarization alternans, a beat-to-beat alternation in action potential duration, has been putatively linked to the onset of cardiac reentry. Anti-alternans control strategies can eliminate alternans in individual cells by exploiting the rate dependence of action potential duration. The same approach, when applied to a common measuring/stimulating site at one end of a cardiac fiber, has been shown to have limited spatial efficacy. As a first step toward spatially distributed electrode control systems, we investigated "off-site" control in canine Purkinje fibers, in which the recording and control sites are different. We found experimentally that alternans can be eliminated at, or very near, the recording site, and that varying the location of the recording site along the fiber causes the node (the location with no alternans) to move along the fiber in close proximity to the recording site. Theoretical predictions based on an amplitude equation [B. Echebarria and A. Karma, Chaos 12, 923 (2002)] show that those findings follow directly from the wave nature of alternans: the most unstable mode of alternans along the fiber is a wave solution of a one-dimensional Helmholtz equation with a node position that only deviates slightly from the recording site by an amount dependent on electrotonic coupling. Computer simulations using a Purkinje fiber model confirm these theoretical and experimental results. Although off-site alternans control does not suppress alternans along the entire fiber, our results indicate that placing the node away from the stimulus site reduces alternans amplitude along the fiber, and may therefore have implications for antiarrhythmic strategies based on alternans termination.
authors.affiliation: Greenberg Division of Cardiology, Department of Medicine, Weill Cornell Medical College, New York, New York 10021, USA. trk2002@med.cornell.edu
authors.forename: Trine
authors.initials: T
authors.lastname: Krogh-Madsen
authors.forename: Alain
authors.initials: A
authors.lastname: Karma
authors.forename: Mark L
authors.initials: ML
authors.lastname: Riccio
authors.forename: Peter N
authors.initials: PN
authors.lastname: Jordan
authors.forename: David J
authors.initials: DJ
authors.lastname: Christini
authors.forename: Robert F
authors.initials: RF
authors.lastname: Gilmour
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000465:Algorithms; D000818:Animals; D003198:Computer Simulation; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008839:Microelectrodes; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000502:physiology*; D010507:Periodicity; D011690:Purkinje Fibers / Q000502:physiology*; D013997:Time Factors