Action of Ryanodine on Mammalian Cardiac Muscle

Abstract

The relationship between stimulation frequency and twitch tension was determined for isolated strips of rat right ventricle. Prolonged perfusion of the tissue in physiological saline solution results in diminished twitch tension at low rates of stimulation without alteration of contractility at high stimulation frequency. These changes, which develop over a period of several hours of perfusion, can be induced within 15 minutes by the addition of ryanodine. The addition of strophanthidin restores the twitch tension-frequency relationship of the long-perfused rat ventricle to normal. However strophanthidin has no effect on the impaired contractility of ryanodine treated ventricle ; and, conversely, the addition of ryanodine to digitalized ventricle abolishes the action of the glycoside. The effects of ryanodine can be reversed by perfusing the muscle in a solution which is deficient in either sodium or potassium. Because of the opposing actions of ryano-dine and the cardiac glycosides, the effect of ryanodine was studied in anesthetized animals with digitoxin-induced cardiac arrhythmias. The intravenous infusion of ryanodine rapidly abolishes the ventricular arrhythmias characteristic of digitalis toxicity. However, the presence of both digitoxin and ryanodine is frequently associated with depression of sinus node activity, and the cardiac cycle is initiated by another focus, probably nodal. The effect on the sinus node may be mediated by the vagus, through a synergistic action of the two drugs, since normal sinus rhythm can be restored by the administration of atropine.