Antiarrhythmic drugs prolong the effective refractory period and depress conduction. To determine the exact role played by these two electrophysiologic effects in the termination of reentry, the effects of disopyramide, flecainide, propafenone and E-4031, a new class III drug, were examined in a canine model of atrial flutter (cycle length 120 ± 4 to 131 ± 3 ms) caused by reentry. Atrial flutter was induced in 32 anesthetized open chest dogs after placement of an intercaval crush. The excitable gap ranged from 9 ± 2% to 11 ± 4% of the basic flutter cycle length. The effective refractory period in the reentrant circuit during atrial flutter was estimated by subtracting the excitable gap from the basic flutter cycle length. Prolongation of flutter cycle length by the test drugs was proportional to the interatrial conduction time (r = 0.87, p < 0.001). Atrial flutter was terminated by each test drug in all dogs except for flecainide and propafenone in one dog each. E-4031 prolonged the refractory period during atrial flutter to 129 ± 6 ms, which did not differ significantly from the flutter cycle length immediately before termination (134 ± 4 ms). The refractory period during atrial flutter after injection of the other drugs was shorter than the flutter cycle length before termination of atrial flutter (for example, flecainide 126 ± 5 vs. 179 ± 11 ms, p < 0.01). These data indicate that E-4031 terminated atrial flutter by abolishing the excitable gap through a greater prolongation of refractoriness relative to a lesser slowing of conduction. The other drugs interrupted atrial flutter by suppressing conduction to a crucial point beyond which propagation of conduction became impossible. © 1991.
Inoue, H., Yamashita, T., Nozaki, A., & Sugimoto, T. (1991). Effects of antiarrhythmic drugs on canine atrial flutter due to reentry: Role of prolongation of refractory period and depression of conduction to excitable gap. Journal of the American College of Cardiology, 18(4), 1098–1104. https://doi.org/10.1016/0735-1097(91)90773-3