STUDY OF THE THERAPEUTIC AND TOXIC EFFECTS OF OUABAIN BY SIMULTANEOUS OBSERVATIONS ON THE EXCISED AND BLOOD-PERFUSED SINOATRIAL NODE AND PAPILLARY MUSCLE PREPARATIONS AND THE IN SITU HEART OF DOGS

¹ Department of Pharmacology and Experimental Therapeutics, Tohoku University School of Medicine, Sendai, Japan

Both the excised sinoatrial node and the excised papillary muscle were cross-circulated with the arterial blood of a donor dog. Ouabain was infused to the donor dog at a constant rate of 1 µg/kg/min. Sinus rate of the sinoatrial node preparation, automaticity atmd contractile force of the papillary muscle preparation and electrocardiogram, heart rate and systemic blood pressure of the donor dog were simultaneously registered. The increase in sinus rate of the sinoatrial node preparation and the arrhythmic contraction of the papillary muscle preparation occurred simultaneously with the appearance of ventricular arrhythmias in the donor dog, both in those dogs anesthetized with morphine and urethane and in those dogs subjected to transection of the spinal cord. The contractile force of the papillary muscle increased until the occurrence of arrhythmic contraction. On the other hand, the steady increase in contractile force was accompanied by a marked decrease in automaticity until the lethal dose was given to adrenalectomized or pithed donor dogs. Neither an increase in sinus rate nor arrhythmic contractions were produced. A similar sequence was observed in a majority of experiments with donor dogs anesthetized with pentobarbital. These observations suggest that ouabain induces depression of ventricular automaticity and an increase in contractile force as the therapeutic effects while sympathetic excitation precipitates ventricular arrhythmias as the toxic effect.