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.
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.
mesh_terms: D000526:Alprenolol / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D003891:Desipramine / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006323:Heart Arrest / Q000139:chemically induced; D006325:Heart Atria; D006339:Heart Rate / Q000187:drug effects; D008012:Lidocaine / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D010477:Perfusion; D010672:Phenytoin / Q000494:pharmacology; D011342:Procainamide / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011802:Quinidine / Q000494:pharmacology; D012849:Sinoatrial Node / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D000889:Anti-Arrhythmia Agents; D013779:Tetrodotoxin; D010672:Phenytoin; D000526:Alprenolol; D008012:Lidocaine; D011433:Propranolol; D011802:Quinidine; D011342:Procainamide; D003891:Desipramine