MECHANISMS OF THE ATRIUM-SPECIFIC POSITIVE INOTROPIC ACTIVITIES OF QUINIDINE-LIKE AND ATROPINE-LIKE AGENTS IN RATS

This study investigated the mechanism of the positive inotropic effect s of class 1 antiarrhythmic agents using electrically stimulated right atria (sinoatrial node excised), left atria and right ventricles of r ats. Quinidine, disopyramide and procainamide produced concentration-d ependent positive inotropic effects on right and left atria; effects o n the right atria were greater than on left atria. At concentration pr oducing positive inotropic effects on atria, the contractions of right ventricles were slightly increased by quinidine, unaffected by disopy ramide and decreased by procainamide. The positive inotropic effects o f quinidine were inhibited by propranolol, reserpine and mecamylamine but not by cocaine, hexamethonium and d-tubocurarine; propranolol also antagonized the positive inotropic effects of disopyramide and procai namide. Bupivacaine, which like quinidine blocks transient outward pot assium current, slightly increased the contractions of right atria but not of left atria and ventricles. The atrium-specific positive inotro pic effects of quinidine were mimicked by atropine, pirenzepine and di methylphenylpiperazinium but not by nicotine, cytisine and butyrylchol ine; the effects of atropine, dimethylphenylpiperazinium and pirenzepi ne were also blocked by propranolol. Quinidine increased the release o f norepinephrine from atria but not from the ventricles; this release was greater from the right than from the left atria. It is concluded t hat quinidine- and atropine-like agents exert atrium-specific positive inotropic effects by blocking muscarinic receptors and permitting a d ominance of acetylcholine effects via a release of norepinephrine from sympathetic nerve terminals.