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Flecainide and the Electrophysiologic Matrix:
Author(s) -
ARNSDORF MORTON F.,
SAWICKI GEORGE J.
Publication year - 1996
Publication title -
journal of cardiovascular electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.193
H-Index - 138
eISSN - 1540-8167
pISSN - 1045-3873
DOI - 10.1111/j.1540-8167.1996.tb00496.x
Subject(s) - flecainide , medicine , purkinje fibers , sodium channel , electrophysiology , cardiology , ischemia , biophysics , antiarrhythmic agent , neuroscience , sodium , chemistry , atrial fibrillation , heart disease , biology , organic chemistry
Flecainide and Excitability. Flecainide was associated with excess mortality distributed virtually equally throughout the period of the Cardiac Arrhythmia Suppression Trial, suggesting the intersection of two events, drug effect and perhaps ischemia. Flecainide's effect on active properties has been studied extensively, but nothing is known of its effects on passive properties or on the balance among active and passive cellular properties that determines cardiac excitability. The multiple microelectrode method of intracellular current application and transmembrane voltage recording was used in sheep Purkinje fibers to determine strength‐and charge‐duration as well as constant current‐voltage relationships and to estimate active properties, liminal length, and cable properties at a normal [K + ] o and in a setting of hyper‐kalemia analogous to that of ischemia. A computer tracked in time the alterations in the active and passive properties relevant to excitability. Flecainide slightly decreased excitability at a normal [K + ] o , primarily by depressing the sodium system with some contributory effect of passive properties. At high [K + ] o , flecainide caused a frequency‐dependent decrease in excitability and conduction, the latter hest interpreted as a failure of the fiber to attain the liminal length requirements to produce a local action potential due primarily to an effect on sodium conductance. Together, the observations suggest that the action potential is the local phenomenon and that the propagated event is the sequential fulfillment of liminal length requirements. The data were interpreted in terms of the electrophysiologic matrix first proposed in detail in this Journal, which indicated that the electrophysiologic universe moved as a system in response to t he drug and a change in [K + ] o , the presumed antiarrhythmic and proarrhythmic electrophysiologic matrices for flecainide were quite similar, and the matrical coufiguration shared characteristics with the matrices of other drugs with know proarrhythmic potential.