Role of asynchronous activation of the ventricular fibres by an ectopic pacemaker in the accidents, especially fibrillation, caused by Ic antiarrhythmic drugs.
Class Ic antiarrhythmic drugs, which are known to slow down conduction in the ventricular muscle, are likely to impair synchrony in activity of the ventricular fibres. Asynchronous activation was first investigated between an ischaemic and a normal area by the simultaneous recording in anaesthetized, open-chest pigs of two left ventricular monophasic action potentials (MAPs) under ventricular pacing at a high rate of 180 beats.min-1. Asynchronous activation was then investigated in the intact myocardium according to the distance separating the recording from the pacing electrode. Furthermore, mechanical effects of left ventricular systole were observed by recording dP/dt(max) and mean arterial blood pressure during the pacing periods. Ischaemia was produced by transient complete occlusion of the left anterior descending coronary artery near its origin; as a result, activation time reached 85 ms in the ischaemic area under flecainide administered iv in a 2.5 mg.kg-1 dose instead of approximately 60 ms in the normal area for fibres equi-distant from the pacing electrode. Similar delays in activation were observed in the intact myocardium, depending on whether the explored region was close to or far from the pacing electrode. In the latter case, the difference in activation time may become markedly greater if the distance or the dose of flecainide are increased. This difference, which possibly exceeds one-third of the MAP duration (practically unchanged by flecainide), may account for the occurrence of fibrillation or the sudden loss of systole mechanical efficacy.
Timour
Q
Q
Department of Medical Pharmacology, Claude Bernard University, Lyon, France.
Aupetit
J F
JF
Loufoua-Moundanga
J
J
Kioueh
I
I
Omar
S
S
Chevrel
G
G
Faucon
G
G
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects*; D005260:Female; D005424:Flecainide / Q000009:adverse effects; D006329:Heart Conduction System / Q000187:drug effects / Q000502:physiology; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology; D010138:Pacemaker, Artificial; D013552:Swine; D014693:Ventricular Fibrillation / Q000139:chemically induced* / Q000209:etiology; D016276:Ventricular Function / Q000187:drug effects / Q000502:physiology*
D000889:Anti-Arrhythmia Agents; D005424:Flecainide