Importance of spatiotemporal heterogeneity of cellular restitution in mechanism of arrhythmogenic discordant alternans
| Autor: | Joseph M. Pastore, Kenneth R. Laurita, David S. Rosenbaum |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Heart Ventricles Guinea Pigs Action Potentials In Vitro Techniques Temporal heterogeneity Heart Conduction System Physiology (medical) Optical mapping Animals Ventricular Function Repolarization Medicine Computer Simulation Simulation based business.industry Body Surface Potential Mapping Cardiac Pacing Artificial Models Cardiovascular Reentry Ventricular Premature Complexes Restitution Kinetics Ventricular Fibrillation Action potential duration Cardiology and Cardiovascular Medicine business Neuroscience |
| Zdroj: | Heart Rhythm. 3:711-719 |
| ISSN: | 1547-5271 |
| Popis: | 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. Objectives 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 Δ-restitution. Δ-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. Conclusion Both temporal and spatial heterogeneities of restitution exist during cellular alternans in the intact heart. Temporal heterogeneities of restitution, quantified by Δ-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. |
| Databáze: | OpenAIRE |
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