title: Influence of the passive anisotropic properties on directional differences in propagation following modification of the sodium conductance in human atrial muscle. A model of reentry based on anisotropic discontinuous propagation.
abstract: Available models of circus movement reentry in cardiac muscle and of drug action on reentrant arrhythmias are based on continuous medium theory, which depends solely on the membrane ionic conductances to alter propagation. The purpose of this study is to show that the anisotropic passive properties at a microscopic level highly determine the propagation response to modification of the sodium conductance by premature action potentials and by sodium channel-blocking drugs. In young, uniform anisotropic atrial bundles, propagation of progressively earlier premature action potentials continued as a smooth process until propagation ceased simultaneously in all directions. In older, nonuniform anisotropic bundles, however, premature action potentials produced either unidirectional longitudinal conduction block or a dissociated zigzag type of longitudinal conduction (a safer type of propagation, similar to transverse propagation). Directional differences in the velocity of premature action potentials demonstrated that anisotropic propagation was necessary for a reentrant circuit to be contained within an area of 50 mm2, even with very short refractory periods. Quinidine produced Wenckebach periodicity, which disappeared after acetylcholine shortened the action potential. Quinidine also produced use-dependent dissociated zigzag longitudinal conduction in the older, nonuniform anisotropic bundles but not in the young, uniform anisotropic bundles. The electrophysiological consequence was that propagation events differed in an age-related manner in response to the same modification of the sodium conductance. The electrical events at microscopic level showed that conditions leading to obliteration of side-to-side electrical coupling between fibers (e.g., aging and chronic hypertrophy) provide a primary mechanism for reentry to occur within very small areas (1-2 mm) due to a variety of propagation phenomena that do not occur in tissues with tight electrical coupling in all directions.
mesh_terms: D000200:Action Potentials; D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology; D005117:Cardiac Complexes, Premature / Q000378:metabolism / Q000503:physiopathology*; D002648:Child; D002675:Child, Preschool; D006325:Heart Atria; D006329:Heart Conduction System / Q000503:physiopathology; D006801:Humans; D007223:Infant; D007473:Ion Channels / Q000502:physiology*; D008012:Lidocaine / Q000494:pharmacology; D008875:Middle Aged; D008955:Models, Cardiovascular; D009132:Muscles / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D011802:Quinidine / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism*
chemical_list: D007473:Ion Channels; D008012:Lidocaine; D012964:Sodium; D011802:Quinidine