title: Spatial correlation analysis of the pharmacological conversion of sustained atrial fibrillation in conscious goats by cibenzoline.
abstract: The nonlinear spatial redundancy and the linear spatial correlation function were used to investigate to what extent non-linearity was involved in the coupling of atrial regions and how organization in activation patterns of sustained atrial fibrillation (AF) had been modified by administration of the class IC agent cibenzoline in the experimental model of sustained AF in instrumented conscious goats. Electrograms were measured in five goats during sustained AF and when the fibrillation interval had been prolonged to about 25%, 50% and 85% (CIB25, CIB50, CIB85) with respect to control. The nonlinear association length and linear correlation length were estimated along the principal axes of two-dimensional correlation maps estimated from the spatial redundancy and the spatial correlation function, respectively. The estimated short axis association length in the right atrium increased already shortly after the start of infusion (CIB25, +61%), and remained significantly different from control during the experiment, including the effects of non-simultaneous interaction. At CIB85 the association length had almost become twice as long with respect to control (increase from 16 to 29 mm, 89%), while in the left atrium changes were less pronounced (increase from 9 to 12 mm, +32%). The linearized association length which was estimated using multivariate surrogate data increased more gradually and was less sensitive to changes in spatial organization. The results of the spatial correlation analysis suggest that the drug-induced nonlinearity in the spatio-temporal dynamics of sustained AF is related to activation patterns which are characterized by extended uniformly propagating fibrillation wavefronts (AF type I). We conclude that cibenzoline enhanced the spatial organization of sustained AF associated with a transition from type II to type I AF activation patterns. This may destabilize the perpetuation of AF since an increase in association length is equivalent to a reduction of atrial tissue mass available to support reentrant circuits. The results are consistent with the hypothesis that larger association lengths result from fewer and larger reentrant circuits. It is argued that effects of diminished curvature of fibrillation wavefronts are anti-arrhythmic under conditions of suppressed excitability imposed by cibenzoline. Termination of AF may be mediated by a mechanism resembling a bifurcation of the dynamics which sets in when the ends of fractionated wavefronts cannot sufficiently curve anymore to maintain a positive balance of newly generated wavelets needed to sustain AF.
authors.affiliation: Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands. hoekstra@lkeb.azl.nl
authors.forename: B P
authors.initials: BP
authors.lastname: Hoekstra
authors.forename: C G
authors.initials: CG
authors.lastname: Diks
authors.forename: M A
authors.initials: MA
authors.lastname: Allessie
authors.forename: J
authors.initials: J
authors.lastname: DeGoede
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000188:drug therapy / Q000503:physiopathology*; D003243:Consciousness; D006041:Goats; D006325:Heart Atria / Q000187:drug effects / Q000503:physiopathology* / Q000648:ultrastructure; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use; D008954:Models, Biological; D017711:Nonlinear Dynamics
chemical_list: D000889:Anti-Arrhythmia Agents; D007093:Imidazoles; C032151:cifenline