Effects of ryanodine in normal dogs and in those with digitalis-induced arrhythmias: Hemodynamic and electrocardiographic studies☆

Abstract The hemodynamic and electrocardiographic effects of ryanodine were studied in normal anesthetized dogs and in those with digitalis-induced ventricular arrhythmias. The electrocardiographic effects of ryanodine may be divided into three sequential overlapping phases: (1) Peaking of the T waves, broadening and flattening of the P waves, loss of the P-R segment, S-T segment depression and sinus slowing; (2) complex paroxysmal supraventricular tachycardias without impairment of A-V conduction; (3) prolonged periods of sinoatrial arrest or bradycardia with A-V block. In all phases the QRS complex was unchanged, and ectopic ventricular beats did not occur. Ryanodine reversed digitalis-induced ventricular arrhythmias in the dog by suppressing ventricular pacemakers without prolonging intraventricular conduction. The conversion to sinus rhythm was usually transient, since complex supraventricular arrhythmias probably attributable to the combined action of the two drugs often supervened. A profound negative inotropic action of ryanodine, previously demonstrated in vitro, was shown to be significant in the intact animal. This was manifested by a significant fall in the cardiac output and a rise in the left ventricular end-diastolic pressure prior to a change in rate or rhythm. The electrocardiographic and negative inotropic effects of ryanodine are similar to those of hyperkalemia, although it is probable that all the observed changes cannot be explained by this mechanism. Since the negative inotropic effects of ryanodine were observed at the same dose required for reversal of the digitalis-induced ventricular arrhythmia, it is likely that the toxicity of this drug precludes its use in the treatment of digitalis intoxication in human beings. However, it may be useful for the study of myocardial metabolism and function.