Effects of antiarrhythmic drugs on canine atrial flutter due to reentry: role of prolongation of refractory period and depression of conduction to excitable gap.
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 less than 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 less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Inoue
H
H
Second Department of Internal Medicine, Tokyo University Hospital, Japan.
Yamashita
T
T
Nozaki
A
A
Sugimoto
T
T
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001282:Atrial Flutter / Q000188:drug therapy* / Q000503:physiopathology; D002304:Cardiac Pacing, Artificial; D004206:Disopyramide / Q000627:therapeutic use; D004285:Dogs; D004562:Electrocardiography; D005424:Flecainide / Q000627:therapeutic use; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology; D010880:Piperidines / Q000627:therapeutic use; D011405:Propafenone / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D012032:Refractory Period, Electrophysiological / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D010880:Piperidines; D011725:Pyridines; C063968:E 4031; D011405:Propafenone; D004206:Disopyramide; D005424:Flecainide