THE SUPRARENAL SYSTEM 237 



followed by death, is larger in proportion to the distance of the 

 site of injection from the heart. 



When injected subcutaneously, ten to fifty times the amount 

 is borne. The lethal dose is about 8 to 10 mg. per kilo in guinea- 

 pigs and rabbits, 5 to 6 mg. in dogs. Frogs tolerate a dose ten 

 times larger in proportion to their weight than rabbits. About 

 .1 mg. injected subcutaneously is fatal to mice weighing 10 to 15 

 grms. Abderhalden and Slavu employed a similar dose of 

 1-suprarenin. These authors found that, in the case of mice, the 

 lethal dose was followed, either by convulsive symptoms lasting a 

 few minutes, or by coma lasting several hours with a terminal 

 fall in temperature. They found the action of d-suprarenin much 

 less toxic, the fatal dose being .1 to .5 grm. The same authors 

 also discovered that, if the animals are previously treated with 

 increasingly large doses of d-suprarenin (.2 to 5 mg.), they 

 acquire a definite tolerance of the 1-component and will bear an 

 amount two to ten times as large as under ordinary conditions. 

 According to Watermann, the immunizing action of d-suprarenin 

 is observed not only in regard to the fatal dose of 1-suprarenin, 

 but also in the case of the dose which provokes glycosuria. 2 mg. 

 1-suprarenin produced little or no sugar in the urine of rabbits 

 which had been previously treated with increasing doses (10 to 

 50 mg.) of d-suprarenin, though under ordinary conditions, such 

 a dose of 1-suprarenin is invariably followed by glycosuria. 



A. Frb'hlich found that the intravenous injection of d-supra- 

 renin (2 to 5 mg.) induced a condition in dogs and cats, in which 

 the blood-pressure was entirely unaffected by the injection of 

 natural adrenalin, by 1-suprarenin in doses of i mg., or 

 by stimulation of the splanchnic nerve. In this state, death by 

 asphyxia is not preceded by any rise in blood-pressure. Accord- 

 ing to Frohlich, the non-toxic d-suprarenin, when given in large 

 doses, combines with certain nervous or muscular portions of the 

 blood-vessel cells and renders them completely inaccessible to the 

 action of 1-suprarenin, to which these cells are, as a rule, very 

 susceptible. Abderhalden, Kautzsch and Miiller were unable to- 

 confirm Frohlich's findings; they believe that the results of his 

 experiments were largely influenced by the presence, in his ani- 

 mals, of relative cardiac insufficiency. 



There is no doubt that the organism acquires a certain 

 tolerance of the toxic action of adrenalin, for, by giving it at 

 intervals of twenty-four hours or longer in increasingly large 

 doses, rabbits, for instance, will take quantities up to .4 mg. 

 without signs of untoward effects. Moreover, it has been 

 definitely proved by Elliott and Durham, that, where animals are 

 under continuous adrenalin treatment, adrenalin antibodies are 

 not formed in the organism. 



When injected into the peritoneum, the lethal dose of adren- 

 alin is about the same as when the injection is given subcutan- 



