Ventricular and atrial electrophysiological effects of a IC antiarrhythmic drug, cibenzoline, in the innervated dog heart. Role of sodium and calcium channels.
The effects of cibenzoline, rightly known as a sodium channel inhibitor (class IC antiarrhythmic drug), were investigated in anaesthetized, closed-chest dogs, on conduction in the contractile fibres, ventricular and atrial, the His-Purkinje system and the atrioventricular node. In ventricular muscle, conduction time was measured between base and apex by two endocavitary electrodes. The other conduction times were obtained from the recording of the His bundle potentials. In addition, effective refractory period was determined by the extrastimulus method in ventricular and atrial muscle and in the atrioventricular node, and sinus rate monitored in the intervals of pacing periods. In the absence of vagal tone, cibenzoline in 4 mg.kg-1 dose prolonged conduction times in the ventricular contractile tissue, His-Purkinje system and atrial contractile tissue to a large extent, but decreasingly from the former to the latter. This prolongation was antagonized by hypernatremia (174 mmol.l-1). In contrast, conduction time in the atrioventricular node, effective refractory periods and sinus rate were very little influenced. In the presence of vagal tone, the prolongation of conduction times in the ventricular contractile tissue. His-Purkinje system and atrial contractile tissue did not differ substantially from previously. It was the same for ventricular effective refractory period. But atrial effective refractory period was then considerably lengthened, while conduction time and effective refractory period in the atrioventricular node were greatly shortened and sinus rate notably accelerated.(ABSTRACT TRUNCATED AT 250 WORDS)
Timour
Q
Q
Laboratoire de Pharmacologie Médicale, Lyon, France.
Aupetit
J F
JF
Loufoua-Moundanga
J
J
Bertrix
L
L
Freysz
M
M
Faucon
G
G
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001283:Atrioventricular Node / Q000187:drug effects; D002036:Bundle of His / Q000187:drug effects / Q000502:physiology; D015220:Calcium Channels / Q000502:physiology*; D002304:Cardiac Pacing, Artificial; D004285:Dogs; D004558:Electric Stimulation; D004562:Electrocardiography; D004594:Electrophysiology; D005260:Female; D006321:Heart / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D012849:Sinoatrial Node / Q000187:drug effects; D015222:Sodium Channels / Q000502:physiology*; D014630:Vagus Nerve / Q000502:physiology
D000889:Anti-Arrhythmia Agents; D015220:Calcium Channels; D007093:Imidazoles; D015222:Sodium Channels; C032151:cifenline