AHEART September 46/

Watanabe, Tetsu, Michiyasu Yamaki, Isao Kubota, Hidetada Tachibana, and Hitonobu Tomoike. Relation between activation sequence fluctuation and arrhythmogenicity in sodium-channel blockades. Am. J. Physiol. 277 (Heart Circ. Physiol. 46): H971–H977, 1999.—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 (2dV/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 6 0.6% (percent total principal component, mean 6 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 6 0.8%). Ventricular fibrillation ensued in all dogs (n 5 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.