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J Pharmacol. 1983 Jul-Sep;14(3):333-49.

Digoxin-induced toxicity and experimental atrioventricular block in dogs. Relation between ventricular arrhythmias and oscillatory afterpotentials.


In anesthetized dogs, digoxin intoxication was performed after and before production of a definitive complete atrioventricular (A-V) block induced by formaldehyde injection in A-V node area, compared to intoxication in dogs in sinus or junctional rhythm. The results showed that digoxin toxicity was decreased in dogs with previous A-V block. This A-V block protective effect was abolished by resetting initial sinus-like frequency with ventricular pacing before digoxin administration. Ventricular arrhythmias were suppressed by production of complete A-V block. The A-V block protective effect can be explained by a lesser myocardial uptake of digoxin because of the low idioventricular frequency. However, ventricular arrhythmias in dogs with A-V block presented similarities both in occurrence and spreading with the development of oscillatory afterpotentials (OAPs) and rhythmical triggered activity demonstrated in isolated digitalis-poisoned Purkinje fibers and ventricular myocardium: the repetitive discharge of toxic foci masked normal idioventricular pacemakers and was interrupted by variable pauses followed by the resumption of either a very slow idioventricular rhythm or a toxic focus. It is suggested that because of the low idioventricular frequency, competition and/or superimposition of slow enhanced diastolic depolarization and OAPs can be electrocardiographically displayed. The terminal event was asystole in dogs with unpaced A-V block, and ventricular fibrillation in dogs with sinus, junctional and paced A-V block rhythms. The asystole (at least 30 seconds of electrical quiescence) may be explained partly as an intense depression of normal idioventricular pacemaker being overdriven by the discharge of toxic pacemakers, and partly as a consequence of the suppression of local autonomic influences in the A-V node area induced by the formaldehyde injection.

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