title: Importance of spatiotemporal heterogeneity of cellular restitution in mechanism of arrhythmogenic discordant alternans.
abstract: BACKGROUND
  Spatially discordant cellular alternans form a substrate for development of unidirectional block and ventricular fibrillation. However, the mechanisms responsible for discordant alternans remain poorly understood. Previous work suggests electrical restitution is critical to the development of alternans in single cells.
  
  
  OBJECTIVE
  The purpose of this study was to investigate the hypothesis that spatial and temporal heterogeneities of restitution underlie the mechanism eliciting discordant alternans.
  
  
  METHODS
  Steady-state pacing was used to elicit concordant cellular alternans in nine Langendorff-perfused guinea pig hearts. A single extrastimulus (S2) was applied every 51st beat following either the even or the odd beat of alternans. The cellular response to S2 was determined using optical mapping to generate action potential duration (APD) restitution curves from 256 ventricular sites for both the even and the odd beats.
  
  
  RESULTS
  Restitution kinetics were temporally heterogeneous during alternans, as restitution curves between the even and the odd beats differed significantly. Temporal heterogeneity was quantified by the average separation of restitution between the two curves, or Delta-restitution. Delta-Restitution was spatially heterogeneous and proportional to the amount of alternans at a given ventricular site. A computer simulation based on the experimental results showed the mechanism of discordant alternans was dependent on both spatial and temporal heterogeneities of restitution.
  
  
  CONCLUSIONS
  Both temporal and spatial heterogeneities of restitution exist during cellular alternans in the intact heart. Temporal heterogeneities of restitution, quantified by Delta-restitution, are proportional to the magnitude of cellular alternans. The combination of spatial and temporal heterogeneities of restitution may underlie the genesis of discordant alternans.
authors.affiliation: Heart and Vascular Research Center, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio 44109, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Pastore
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Laurita
authors.forename: David S
authors.initials: DS
authors.lastname: Rosenbaum
mesh_terms: D000200:Action Potentials; D000818:Animals; D018780:Body Surface Potential Mapping; D002304:Cardiac Pacing, Artificial; D003198:Computer Simulation; D006168:Guinea Pigs; D006329:Heart Conduction System / Q000503:physiopathology; D006352:Heart Ventricles / Q000503:physiopathology*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008955:Models, Cardiovascular; D014693:Ventricular Fibrillation / Q000503:physiopathology*; D016276:Ventricular Function; D018879:Ventricular Premature Complexes