240 INTERNAL SECRETION 



The most conspicuous of the toxic effects of adrenalin is that 

 which it exercises upon the circulatory organs. The repeated 

 injection of adrenalin produces serious changes in the heart ; 

 hypertrophy of the left ventricle, myositis fibrosa, ischa^mic in- 

 farction, foci which have undergone hyaline degeneration, and 

 necrosed patches, have all been observed. 



Of the changes effected by suprarenal extract, or by adren- 

 alin, upon the circulatory apparatus, those which may be experi- 

 mentally induced in the arteries have received the most attention. 

 It is expedient to the present purpose to enter rather more fully 

 into this subject. 



Josue was the first to show, in 1902, that the repeated injection 

 of adrenalin into the veins of rabbits produces atheroma of the 

 vessels. Jores had previously tried to produce changes in the 

 vessel walls by means of suprarenal tabloids given by the mouth, 

 but his experiments were quite unsuccessful. 



Later, experiments were carried out upon animals of varying 

 species with the different suprarenal preparations; with adrenalin 

 obtained from the suprarenal and with synthetic preparations, 

 such as methylaminoacetopyrocatechin, by Sturli ; and with syn- 

 thetic suprarenin and its components, 1- and d-suprarenin, by 

 Biedl. 



Experiments with dogs have produced somewhat variable 

 results. Fischer and Mori, as well as Pearce and Stanton, 

 obtained negative results ; while Tarantini and Braun found that 

 the intravenous injection of adrenalin was followed by vascular 

 changes similar to those seen in rabbits immediately after such 

 injection. According to Loeper, Lissauer, v. Hansemann and 

 Boveri, the symptoms are intensified by feeding the animals with 

 calcium ; moreover, animals, the normal diet of which is rich in 

 calcium, such as the hare, horse and cow, are more susceptible 

 to vascular changes than animals whose normal food contains 

 but little calcium (dog, cat). 



The rabbit is a very reliable subject for such experiment,* 

 and has been employed in the great majority of cases. It is 

 evident that, in the first place, the appearance of changes in the 

 vessel walls is dependent upon the manner in which the drug is 

 exhibited. The results of subcutaneous injection have occasion- 

 ally been positive, but far more often negative, in character. After 

 intratracheal injection, Kiilbs observed typical changes in the 

 aorta; Fischer found that intraperitoneal injection was not fol- 

 lowed by such changes ; Erb noticed slight changes in the aorta ; 

 d'Amato observed similar changes after the introduction of 

 Vassale's preparation, ' paraganglin," into the stomach; and 

 Tarantini obtained only negative results by the latter method. 



' Klotz and Bennecke think that the large calcium contents of rabbits' 

 blood is significant in this connection. 



