Class Ic antiarrhythmic drugs and myocardial ischaemia: study in the pig heart in situ.
The effects of three Ic antiarrhythmic drugs, flecainide, propafenone and cibenzoline, were investigated in anaesthetized, open-chest pigs, in a left ventricular area, during pacing at a constant high rate (180 beats min-1), in the absence and the presence of ischaemia. Ischaemia was produced by transient complete occlusion of the left anterior descending coronary artery 1-1.5 cm from its origin. In addition to surface electrocardiogram, conduction time and monophasic action potential were recorded in the contractile fibres. Measurement of the effective refractory period was added in the absence of ischaemia. In this event, flecainide and propafenone, each in a dose of 2.5 mg kg-1 i.v. and cibenzoline, 2.0 mg kg-1, i.v., considerably lengthened (by 50-90%) conduction time, but did not affect or hardly affected the duration of the monophasic action potential or the effective refractory period. Thus, it seems that these Ic antiarrhythmic drugs enhance the prolongation of conduction time by 60% and do not prevent the 30% shortening of monophasic action potential caused by ischaemia: contrary to expectation, they produced a large reduction (from about 120 to 25 s) in the onset time of fibrillation due to ischaemia. Thus, they manifested profibrillatory properties (more pronounced than those of other class I antiarrhythmic drugs), which might be explained by their potent action on depolarization with almost total absence of action on repolarization.
Timour
Q
Q
Laboratoire de Pharmacologie Médicale, Lyon, France.
Aupetit
J F
JF
Loufoua-Moundanga
J
J
Gerentes-Chassagne
I
I
Kioueh
I
I
Faucon
G
G
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003327:Coronary Disease / Q000503:physiopathology*; D003331:Coronary Vessels; D005260:Female; D005424:Flecainide / Q000494:pharmacology; D006329:Heart Conduction System / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D011405:Propafenone / Q000494:pharmacology; D013552:Swine; D014693:Ventricular Fibrillation
D000889:Anti-Arrhythmia Agents; D007093:Imidazoles; D011405:Propafenone; D005424:Flecainide; C032151:cifenline