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  • Title: Comparative study of the action of antiarrhythmic drugs on sinoatrial nodal pacemaker activity and contractility in the isolated blood-perfused atrium of the dog.
    Author: Chiba S.
    Journal: Clin Exp Pharmacol Physiol; 1976; 3(6):599-608. PubMed ID: 1009695.
    Abstract:
    1. The effects of five antiarrhythmic drugs (quinidine, procainamide, lignocaine, phenytoin and propranolol) were studied on pacemaker activity in the sinoatrial node and on contractility in twenty-three isolated, blood-perfused atrium preparations of dogs. Each drug was administered directly into the cannulated sinus node artery of an isolated atrium over a period of 4 s. 2. Quinidine produced negative chronotropic and inotropic effects. Occasionally, higher doses induced a biphasic inotropic effect, an initial negative phase being followed by an increase in contractility. 3. Three response patterns to procainamide were observed: negative chronotropic and inotropic effects; biphasic effects, initially negative chronotropic and inotropic effects being followed by positive effects; a biphasic inotropic effect and a negative chronotropic effect. The third pattern was most frequently produced by relatively high doses. 4. Lignocaine, phenytoin and propranolol induced dose-related negative chronotropic and inotropic effects. 5. All five of the antiarrhythmic drugs used caused sinus arrest in high doses. 6. Procainamide-induced positive chronotropic and inotropic effects were significantly inhibited by treatment with alprenolol or nadolol, but not by tetrodotoxin or desipramine. 7. These results indicate that procainamide-induced positive chronotropic and inotropic effects may involve an adrenergic mechanism.
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