Arrhythmogenicity of antiarrhythmic drugs and intraventricular conduction disorders: possible aggravation by myocardial ischemia--study in the porcine in situ heart.
The effects of three antiarrhythmic drugs were investigated in anesthetized, open-chest pigs, in a left ventricular area, under pacing at a constant high rate (180 beats/min), in the absence and presence of ischemia. Ischemia was produced by transient complete occlusion of the left anterior descending coronary artery near its origin. In addition to the surface electrocardiogram, conduction time and monophasic action potential were recorded in the contractile fibers. In the absence of ischemia, intravenous flecainide and propafenone 2.5 mg/kg, and intravenous cibenzoline 2.0 mg/kg considerably lengthened conduction time (by 50-90%) but had no significant effect on the monophasic action potential duration. Consequently, the cited antiarrhythmic drugs enhance the prolongation of conduction time by 60% but do not limit the 30% shortening of the monophasic action potential caused by ischemia. Contrary to what was expected, they largely reduced the time to onset of the fibrillation due to ischemia from about 120 to 25 seconds. Thus, they manifested profibrillatory properties (more pronounced than those of other antiarrhythmic drugs of class I), which might be explained by their potent action on depolarization.
Aupetit
J F
JF
Département de Cardiologie, Hôpital Saint-Joseph, Lyon, France.
Timour
Q
Q
Larbre
J P
JP
Loufoua-Moundanga
J
J
Kioueh
I
I
Lopez
M
M
Faucon
G
G
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004562:Electrocardiography; D005260:Female; D005424:Flecainide / Q000009:adverse effects / Q000494:pharmacology; D006329:Heart Conduction System / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000009:adverse effects / Q000494:pharmacology; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D011405:Propafenone / Q000009:adverse effects / Q000494:pharmacology; D013552:Swine
D000889:Anti-Arrhythmia Agents; D007093:Imidazoles; D011405:Propafenone; D005424:Flecainide; C032151:cifenline