[Arrhythmogenic risk of antiarrhythmic drugs: study with class Ic drugs during myocardial ischemia].
The effects of three Ic antiarrhythmic drugs were investigated in anaesthetized, open-chest pigs, in a left ventricular area under pacing at constant high (180/min) rate, outside and during an ischaemia produced by temporary complete occlusion of the left anterior descending coronary artery, 1-1.5 cm from its origin. In addition to surface ECG, conduction time and monophasic action potential were recorded in the contractile fibres. Measurement of effective refractory period was added outside the periods of ischaemia. In this event, flecainide and propafenone, in 2.5 mg/kg dose, and cibenzoline, in 2.0 mg/kg dose, i.v. injected, lengthened considerably (50 to 90%) conduction time, but did not affect or hardly affected monophasic action potential and effective refractory period. During ischaemia, they did not hinder the abbreviation of monophasic action potential (30%) and reduced to a large extent (about 120 to 25 s) the onset time of fibrillation. The profibrillatory effect of Ic antiarrhythmic drugs, certainly more pronounced than those of other antiarrhythmic drugs, might be explained by their potent action on depolarization of the contractile fibres coincident with an almost total absence of action on repolarization.
Faucon
G
G
Laboratoire de Pharmacologie médicale, Faculté Grange-Blanche, Lyon.
Aupetit
J F
JF
Gerentes-Chassagne
I
I
Loufoua-Moundanga
J
J
Larbre
J P
JP
Timour
Q
Q
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000503:physiopathology; D002304:Cardiac Pacing, Artificial; D003327:Coronary Disease / Q000188:drug therapy*; D004195:Disease Models, Animal; D005424:Flecainide / Q000008:administration & dosage / Q000009:adverse effects*; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects*; D007275:Injections, Intravenous; D011405:Propafenone / Q000008:administration & dosage / Q000009:adverse effects*; D013552:Swine
D000889:Anti-Arrhythmia Agents; D007093:Imidazoles; D011405:Propafenone; D005424:Flecainide; C032151:cifenline
Le risque arythmogène des antiarythmiques: étude avec les produits de classe Ic au cours de l'ischémie myocardique.