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Although the effect of the extract of the posterior lobe of the pituitary gland upon the mammalian heart has been studied by a number of investigators, the results have not been uniform. In the first study of the action of pituitary extracts, Oliver and Schafer (1895) found that with the vagi intact no inhibition of the heart took place, but that with the vagi cut there was a slight diminution in heart rate. Howell (1898) obtained a definite slowing with the vagi intact. When the vagi were cut or under the influence of atropine, a slowing of cardiac rate of lesser degree was observed, and he attributed the action of the drug to an influence not only on the cardio-inhibitory center but also to an effect on the heart muscle or the intrinsic nervous mechanism. Von Cyon (1898) obtained similar results. Hedbom (1898), Cleghorn (1899), and Dale (1909), using isolated mammalian heart preparations, found that the rate was lowered under the influence of pituitary extracts, indicating that the action was in part at least direct on the myocardium. Schafer and Vincent (1900) observed but little slowing of the rate when the vagi were paralyzed by atropine, and occasionally no fall in rate even with the vagi intact. They concluded, however, on the basis of the experiments of Howell and of Cleghorn, that in addition to the vagal action, there must be a direct effect on the cardiac muscle. Garnier and Thaon (1906) ascribed the action wholly to an influence through the vagi, for no slowing occurred after these nerves were sectioned. Wiggers (1911) obtained slowing upon perfusion of the drug through the isolated heart; while with the heart in situ, a variety of results was seen. In 217

THE ACTION OF PITUITARY EXTRACT ON THE HEART OF THE UNANESTHETIZED DOG