ORGANOTHERAPY AND HORMONOTHERAPY 125 



All these effects pass off rapidly, the blood-pressure falling within a few 

 minutes to its original level, or even lower, while the heart first goes back 

 to its former rate and then as a rule exceeds it. This acceleration is due 

 to the fact that the accelerator action persists longer than the rise in 

 blood-pressure, and is no longer overcome nor masked by the vagus stimula- 

 tion. The fall in blood-pressure below its original level is the result of 

 a late vasodilation. 40 The stimulation of the accelerator endings is best 

 studied on the isolated surviving mammalian heart, where it manifests 

 itself by a striking increase in the rate, force, and extent of the contrac- 

 tions. This effect manifests itself in vigorously beating, as well as in 

 feeble exhausted hearts. In the intact mammal, large doses frequently 

 cause premature (ectopic) ventricular contractions, and under certain 

 conditions ventricular fibrillation. This latter is especially liable to occur 

 under light chloroform anesthesia. 41 Rothberger and Winterberg found 

 that in dogs epinephrin caused the same electrocardiographic changes as 

 accelerator stimulation. 



The behavior of the different arteries under the influence of epinephrin 

 has been intensively studied by many observers. Using segments of iso- 

 lated arteries, Langendorff found that epinephrin caused contraction of 

 all the arteries of the body, with the exception of the coronary vessels, 

 which are dilated. His findings have in most particulars been confirmed 

 by other observers. In the intact mammal, however, conditions are not 

 so simple. Numerous investigations, notably those of Hoskins (c), and of 

 Hartman (&), have shown that with ordinary doses there is constriction of 

 the splanchnic and cutaneous vessels, and dilatation of the vessels of the 

 lungs and voluntary muscles. 



The clinical use of epinephrin in the treatment of hemoptysis renders 

 it desirable that we should know how this drug affects the pulmonary 

 circulation. Studies on the isolated artery by Langendorff and the per- 

 fusion experiments of Plunder and of Wiggers (a) (1909) show that these 

 arteries follow the general rule of responding to epinephrin by contrac- 

 tion. However, Brodie and Dixon found that very small doses caused 

 dilation, and Hartman and Hoskins, using the intact mammal, with 

 ordinary intravenous doses, also found a vasodilating effect. Schafer and 

 Lim, using intravenous and intra-arterial injections, found in rabbits a 



40 Cannon and Lyman (a) (1912-13) have found that in cats very small doses usu- 

 ally cause a fall in the blood-pressure, in a series of clinical observations on the 

 effects of oral administration of epinephrin, I have occasionally seen a slight but dis- 

 tinct fall in blood-pressure without any preceding rise. It is possible that this fall 

 is analogous to that observed by Cannon and Lyman. 



41 Levy (a) (b) (c) and Lewis found that in cats, which had been sufficiently 

 deeply anesthetized by chloroform, subsequent light chloroform anesthesia so affected 

 the heart muscle that accelerator stimulation caused the development of ventricular 

 fibrillation. As the action of epinephrin on the heart is identical with that of accel- 

 erator stimulation, it is not surprising that injection of epinephrin brings on this 

 condition. The clinical importance of this fact must not be overlooked when using 

 epinephrin in threatened chloroform death. 



