132 the venom of heloderma. 



Effect of Pilocarpine and Atropine on the Production of Ulcers. 



On the basis of these anatomical facts, we extended our worlc in order to 

 clear up the causation of these ulcers by experimental means. We studied the 

 influence of gastric secretion, the effect of the neutralization of the latter by 

 sodium-carbonate solution, the relation of these ulcers to the distribution of the 

 vessels, and the effect of thrombosis. Inasmuch as pilocarpine is supposed to 

 increase gastric secretion, and atropine to lessen it, it was of interest to observe 

 in what way they could modify the ulceration produced by venom. 



Added interest was attached to these experiments, as the possibility of the 

 excretion of venom into the stomach as a cause of the ulceration had to be con- 

 sidered. We therefore injected three sets of animals, one with venom alone, 

 one with atropine and venom, and one with pilocarpine and venom, and ob- 

 served them under identical conditions. We found that those animals which 

 received pilocarpine in addition to venom showed markedly increased ulcera- 

 tion and hemorrhage. In fact, the most marked cases of ulceration and hemor- 

 rhage seen in this work were observed after the combined use of pilocarpine and 

 venom. For instance, in the case of guinea-pig 109 the stomach was com- 

 pletely covered with a great number of ulcers and hemorrhagic areas varying 

 from 1 to 7 mm. in diameter. Atropine also increased the tendency toward 

 ulceration, but this was not nearly as well marked as in the instance of pilocar- 

 pine. The addition of either substance, therefore, but especially of pilocarpine, 

 to venom, increases the gastric ulceration. These results suggested the ques- 

 tion as to what might be the effect of these alkaloids on the stomach without 

 the addition of venom. 



We therefore administered lethal doses of atropine and pilocarpine with- 

 out venom. As much as 3.7 grains of atropine sulphate and 8 grains of pilo- 

 carpine hydrochloride were given subcutaneously in fractional doses with suffi- 

 cient frequency to keep the animal in a markedly toxic state for several hours 

 before death. In the two pilocarpine animals distinct ulceration and hemor- 

 rhage were present, while in two out of six atropine animals hemorrhagic ero- 

 sion, and in one of these also a typical small ulcer, was found. Three of the 

 six guinea-pigs that received atropine died so soon after the injection that the 

 time was insufficient for an ulcer to form. In these experiments also the 

 ulcers were formed if the animals had been in a markedly toxic state several 

 hours before death. 



Inasmuch as the ulceration and hemorrhage produced differed only quan- 

 titatively in these cases, we tried various other poisons, observing the precau- 

 tion to inject the substance with sufficient frequency to keep the animal in a 

 markedly toxic state for several hours before producing death. Paraldehyde, 

 chloroform, 10 per cent phenol, and a saturated solution of magnesium chloride 

 were all tried, as well as sodium fluoride and copper sulphate. Without going 

 into detailed description, we may state that, with every poisonous substance, we 

 were able to obtain, under proper conditions, some gastric lesion. This latter 

 varied from distinct ulceration in the paraldehyde animals to the occasional 

 hemorrhagic erosions seen in the chloroform or magnesium-sulphate animals. 



