Intracoronary flecainide induces ST alternans and reentrant arrhythmia on intact canine heart: A role of 4-aminopyridine-sensitive current.
BACKGROUND
The electrical alternans shown on an ST segment, ST alternans, is known as one of the most important predictors of ventricular fibrillation (VF). It has also been reported that sodium channel inhibition changes action potential configuration, especially on the repolarization phase. Thus, the sodium channel blocker may produce ST alternans and trigger reentrant arrhythmia.


RESULTS
A sodium channel blocker (disopyramide, lidocaine, or flecainide) was infused selectively into the left anterior descending coronary artery in anesthetized, open-chest dogs. Sixty unipolar electrograms were simultaneously recorded from the entire cardiac surface of the heart. The amplitude of ST alternans (STa) was determined as the difference in the ST-segment magnitude between 2 consecutive electrograms. We accepted the greatest STa among 60 leads for evaluation. High-dose flecainide (100 microg. kg-1. min-1) increased STa and evoked a spontaneous VF. The STa in high-dose flecainide loading (8.7+/-3.4 mV; mean+/-SEM) was significantly greater than that in disopyramide or lidocaine (0. 9+/-0.4 and 0.8+/-0.2 mV, P<0.05). Treatment of 4-aminopyridine (4-AP) suppressed the increase in STa and the occurrence of VF evoked by flecainide, while E4031 or verapamil did not inhibit those.


CONCLUSIONS
Flecainide caused the ST alternans that was closely correlated to the occurrence of VF. Because the ST alternans was suppressed by 4-AP treatment, a 4-AP-sensitive current such as Ito or Isus may play an important role on this phenomenon.
Tachibana
H
H
First Department of Internal Medicine, Yamagata University School of Medicine, Yamagata, Japan.
Yamaki
M
M
Kubota
I
I
Watanabe
T
T
Yamauchi
S
S
Tomoike
H
H
D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D003331:Coronary Vessels; D004206:Disopyramide / Q000494:pharmacology; D004285:Dogs; D004562:Electrocardiography; D005424:Flecainide / Q000008:administration & dosage*; D007267:Injections; D008012:Lidocaine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects; D014693:Ventricular Fibrillation / Q000139:chemically induced; D014700:Verapamil / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D010880:Piperidines; D011725:Pyridines; D015222:Sodium Channels; C063968:E 4031; D008012:Lidocaine; D015761:4-Aminopyridine; D014700:Verapamil; D004206:Disopyramide; D005424:Flecainide