Widening of the Excitable Gap During Pharmacological Cardioversion of Atrial Fibrillation in the Goat

Abstract

Pharmacological cardioversion of AF cannot be explained by prolongation of WL(AF). An alternative explanation for the antifibrillatory effect of class I and III drugs may be a widening of the temporal excitable gap.

Antiarrhythmic and Electrophysiologic Effects of Flecainide on Acutely Induced Atrial Fibrillation in Healthy Horses

“…However, in 2 horses the termination times were strikingly short and correlated with very limited increases in AFCL, indicating a questionable drug‐related termination of AF. However, in the majority of horses, the flecainide‐induced increase in AFCL corresponded well with results reported by others 2, 17, 24, 27. A single study investigating flecainide‐induced changes in AFCL in horses with spontaneous AF reported comparable increases, nevertheless none of the treated horses cardioverted in response to treatment 2.…”

“…Still, despite the lack of aERP prolongation at the atrial rates measured in the present study, we cannot rule out possible increases in aERP during the rapid rates typical of AF. Our observations are in agreement with results from studies conducted in goats where aERP was unaffected, AFCL increased, and AF vulnerability unchanged by flecainide 17, 24. The variable flecainide‐induced changes in aERP may be related to species differences and species‐specific atrial ion channel composition.…”

“…Our study identified no flecainide‐induced changes in aERP, indicating that flecainide did not have an influence on atrial repolarization at the chosen stimulation rates. Depending on the model, flecainide has been reported to have variable effects on aERP in vivo 16, 17, 18, 19, 20. In humans, some reported a slight but not significant flecainide‐induced increase in aERP, whereas others reported significant and use‐dependent increases 20, 34.…”

“…However, the exact pharmacologic mechanisms are not fully understood. In vivo studies have produced conflicting results with regard to flecainide‐induced changes in atrial effective refractory period (aERP) 16, 17, 18, 19, 20. Flecainide may slow the atrial activation rate and eventually terminate AF by decreasing excitability, increasing the size and decreasing the number of re‐entrant circuits,18 primarily by widening the temporal excitable gap (the difference between AF cycle length [AFCL] and aERP during AF),16, 17 by changing the appearance of the rotating wavefront or some combination of these effects 21, 22, 23.…”

“…Flecainide may slow the atrial activation rate and eventually terminate AF by decreasing excitability, increasing the size and decreasing the number of re‐entrant circuits,18 primarily by widening the temporal excitable gap (the difference between AF cycle length [AFCL] and aERP during AF),16, 17 by changing the appearance of the rotating wavefront or some combination of these effects 21, 22, 23. In animal tachypacing models and in human AF patients, flecainide caused increased AFCL, decreased conduction velocity and caused a minor tachycardia‐dependent increase in aERP 17, 24, 25, 26, 27, 28, 29. In horses, a marked flecainide‐induced increase in AFCL has been reported,2 but the effects of flecainide on aERP, AF duration, and AF vulnerability have not yet been investigated.…”