Prolongation of intraventricular conduction time associated with fatal [correction of fetal] impairment of defibrillation efficiency during treatment with class I antiarrhythmic agents.
To test whether fatal deterioration of defibrillation efficiency during antiarrhythmic therapy can be prevented by avoiding extreme decrease in ventricular prevented by avoiding extreme decrease in ventricular conduction or toxic plasma drug levels, we determined the defibrillation threshold (DFT) before and during infusion of incremental doses of disopyramide (n = 8), mexiletine (n = 9), or flecainide (n = 9) in anesthetized dogs. Disopyramide did not alter DFT [from 4.4 +/- 1.5 to 4.4 +/- 1.6 J (3.1 +/- 1.2 micrograms/ml)]. Mexiletine tended to increase DFT [from 4.6 +/- 1.2 to 6.1 +/- 2.0 J (1.8 +/- 0.6 micrograms/ml); p < 0.05], and defibrillation eventually was unsuccessful in 3 of the 9 dogs. Although the plasma mexiletine level before refractory fibrillation was far beyond the human therapeutic range, prolongation of intraventricular conduction time (CT) was moderate (16 +/- 3%). Flecainide increased DFT from 4.2 +/- 1.3 to 6.1 +/- 1.5 J at a plasma level of 1.04 +/- 0.37 micrograms/ml (p < 0.0005). In 3 of 5 dogs that developed refractory fibrillation, plasma flecainide level before terminal ventricular fibrillation (VF) was not toxic, but prolongation of CT in the 5 dogs was remarkable (30 +/- 9%). Thus, VF resistant to defibrillation is not necessarily associated with both toxic plasma drug level and remarkably decreased conduction. Reliability of these valuables as indicators of fatally deteriorated defibrillation efficiency may vary among antiarrhythmic agents.
Murakawa
Y
Y
Second Department of Internal Medicine, University of Tokyo, Japan.
Inoue
H
H
Kuo
T T
TT
Sezaki
K
K
Nakajima
T
T
Usui
M
M
Yamashita
T
T
Ajiki
K
K
Oikawa
N
N
Sugimoto
T
T
D000704:Analysis of Variance; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use / Q000633:toxicity*; D017147:Defibrillators, Implantable; D004206:Disopyramide / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use / Q000633:toxicity; D004285:Dogs; D004594:Electrophysiology; D005260:Female; D005424:Flecainide / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use / Q000633:toxicity; D006321:Heart / Q000187:drug effects; D006329:Heart Conduction System / Q000187:drug effects*; D008297:Male; D008801:Mexiletine / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use / Q000633:toxicity; D009206:Myocardium / Q000473:pathology; D014693:Ventricular Fibrillation / Q000517:prevention & control*
D000889:Anti-Arrhythmia Agents; D008801:Mexiletine; D004206:Disopyramide; D005424:Flecainide