Relation between activation sequence fluctuation and arrhythmogenicity in sodium-channel blockades.
To examine the correlation between activation sequence fluctuation and arrhythmogenicity, we investigated temporal changes in the activation sequence by measuring activation times [negative first derivative of voltage over time (-dV/dt) in QRS] from the entire heart in 18 dogs. The heart was paced by constant atrial stimulation. The character of the activation sequence fluctuation was established by a principal component analysis, in which the first principal component was defined as a stable component of the sequence and the second or third component as a fluctuated component. Steady state contained 2.2 +/- 0.6% (percent total principal component, mean +/- SD) of fluctuated components, which appeared in a beat-by-beat manner (activation sequence alternans). Activation sequence alternans was observed only during flecainide administration and not during lidocaine or disopyramide administration. Fluctuated components at a high dose of flecainide significantly increased (3.3 +/- 0.8%). Ventricular fibrillation ensued in all dogs (n = 6) exposed to flecainide after an increase in activation sequence alternans. In conclusion, flecainide evoked local activation sequence alternans. This phenomenon correlated with the occurrence of ventricular fibrillation.
Watanabe
T
T
First Department of Internal Medicine, Yamagata University School of Medicine, Yamagata 990-9585, Japan. tewatana@med.id.yamagata-u.ac.jp
Yamaki
M
M
Kubota
I
I
Tachibana
H
H
Tomoike
H
H
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000503:physiopathology*; D004285:Dogs; D005424:Flecainide / Q000494:pharmacology / Q000627:therapeutic use; D006321:Heart / Q000502:physiology*; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000502:physiology*; D014693:Ventricular Fibrillation / Q000188:drug therapy / Q000503:physiopathology; D016276:Ventricular Function
D000889:Anti-Arrhythmia Agents; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D005424:Flecainide