Ventricular and atrial electrophysiological effects of a IC antiarrhythmic drug, cibenzoline, in the innervated dog heart

Abstract

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)

Enhancement by ischemia of the risk of cardiac disorders, especially fibrillation, in regional anesthesia with bupivacaine

“…The contractile fibers possessing the most negative potential exhibit the most delayed activation. The behavior of bupivacaine resembles that of the IC antiarrhythmic drugs, such as flecainide (21)(22)(23)(24)(25), which depress intraventricular conduction to a great extent on account of a strong influence on sodium channel in moderate doses which have little effect on repolarization. As these drugs have been shown by multicenter, randomized, placebo-controlled trials (26,27) to be likely to increase the incidence of sudden death, instead of decreasing it as expected, similar accidents were possible with bupivacaine.…”

“…However, the occurrence of ventricular fibrillation is not impossible at less high levels, if tachycardia or ischemia is associated, since this accident has been reported with flecainide and related drugs when these drugs had failed to control fast ectopic rhythms or had been administered to patients shortly after an acute myocardial infarction. Indeed, the higher the rate of impulses, the more pronounced is the inhibition of conduction caused by bupivacaine (6,21), as by any sodium channel blocking drug (22,23). However, the depression is particularly enhanced by ventricular tachycardia because of the impulse propagation in the contractile fibers, which are more sensitive to sodium blockers than the specialized fibers.…”

“…Depolarization is therefore secondary to the loss by the fibers of potassium, which accumulates in the clefts as early as the first seconds of the rise in pacing rate (30), and to the retention of sodium and calcium in the cellular medium (31, 32). By virtue of the relationship established by Weidmann (33), the decrease in resting potential enhances the slowing down of conduction due to the bupivacaine-induced reduction of sodium conductance, even though it is not sufficient to impair normal conduction (22,23). Nevertheless, fibrillation is rarely produced by the joint influence of bupivacaine and tachycardia.…”

Ischaemia‐induced loss or reversal of the effects of the class I antiarrhythmic drugs on vulnerability to fibrillation

“…The critical level of conduction impairment for generating fibrillation is reached sooner when the inhibitory properties of the drug on conduction are more pronounced. Conceivably, Ic drugs which possess such properties (Lang et al , 1988; Timour et al , 1989) are known to be the class I drugs which give rise to the greatest number of fibrillatory accidents (Winkle et al , 1981; Velebit et al , 1982). Conversely, the risk of fibrillation seems to be less with Ib drugs, such as lignocaine which has little influence on conduction (Gerstenblith et al , 1978; Badui et al , 1981; Carson & Dresel, 1983).…”

Cardiac electrophysiologic measurements in dogs before and after intravenous administration of atropine and propranolol

“…Atrioventricular nodal conduction is equally influenced by the 2 arms of the ANS , and responses of the AV node are dependent on a highly complex interaction between relative ANS tone , timing and nature of vagal input , and baseline heart rate . * 4 Added to this complexity are the effects of certain preanesthetic agents , such as butorphanol , in increasing vagal tone , changes in ANS tone induced by general anesthesia ( deeper planes of general anesthesia can abolish vagal tone ) , and potential direct effects of volatile anesthetics to increase AV nodal refractoriness and conduction delay 6,22. Interestingly , these direct anesthetic effects may be masked in vivo by adrenergic and reflexmediated effects 22.…”