Termination of a tachyarrhythmia by flunarizine is not a specific marker for a triggered mechanism.
BACKGROUND
Prior studies have indicated that tachyarrhythmia termination by flunarizine demonstrates a triggered mechanism. This concept was not confirmed in atrial tachyarrhythmias.


OBJECTIVE
The purpose of this study was to test the hypothesis that flunarizine will not terminate reentrant atrial flutter (AFL).


METHODS
We administered flunarizine (2 mg/kg intravenously over 2 minutes) in 11 episodes of reproducibly inducible, sustained AFL in eight canines with sterile pericarditis. If flunarizine terminated AFL, we studied AFL reinducibility. We also studied pacing thresholds, refractoriness, and intra-atrial conduction time during closed-chest studies and pacing at selected cycle lengths (CLs) from selected sites before and after flunarizine administration. Atrial mapping (510 electrodes) assessed the epicardial activation sequence during AFL and its termination in six episodes. Four AFL episodes were studied in the closed-chest state.


RESULTS
Flunarizine increased AFL CL in all episodes (mean 21 ms; range 7-49 ms), which is explained by slowing conduction in the AFL reentrant circuit, principally in the area of slow conduction. AFL was terminated in 10/11 episodes after drug initiation (mean 3.7 minutes; range 0.5-6.5 minutes) by block in the area of slow conduction. AFL was then not immediately reinducible until >20 minutes after drug administration. Flunarizine had no meaningful effect on atrial pacing thresholds for capture or refractoriness and only affected conduction time in the area of slow conduction in the reentrant circuit.


CONCLUSIONS
Flunarizine (1) causes progressive slowing and block in the area of slow conduction of the AFL reentrant circuit in the canine sterile pericarditis model and (2) is effective in terminating reentrant AFL and so is not a specific marker for a triggered mechanism.
Vitebskiy
Sergey A
SA
Case Western Reserve University, University Hospitals Case Medical Center, Cleveland, Ohio 44106, USA.
Khrestian
Celeen M
CM
Waldo
Albert L
AL
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001282:Atrial Flutter / Q000188:drug therapy*; D004285:Dogs; D005444:Flunarizine / Q000627:therapeutic use*; D006329:Heart Conduction System / Q000187:drug effects / Q000502:physiology
D000889:Anti-Arrhythmia Agents; D005444:Flunarizine