Guanidine Retention and Calcium Reserve as Antagonistic Factors in Carbon Tetrachloride and Chloroform Poisoning. ∗

Abstract

An earlier note 1 reported the rather empirical observation that dogs on a lean meat diet can be made either highly resistant or susceptible to carbon tetrachloride intoxication by adding or withholding calcium salts for a few days previous to the administration of carbon tetrachloride. Furthermore calcium therapy was found highly effective in the treatment of cases of poisoning.

The intoxication produced in susceptible dogs was described in the earlier note and is characterized by gastro-intestinal irritation, nervous disturbances and convulsions, followed by weakness, depression, and death. There is a retention of bile pigments in the blood and a hypoglycemia which usually becomes extreme before death and which seems in most cases to be the immediate cause of death. The level of total calcium in the blood is usually within normal limits, nevertheless either a lack of or excessive demand for calcium ions seems to be indicated by the relief afforded by the furnishing of extra available calcium. It was at first suggested that a depression of ionized calcium due to combination with bile pigments might account for the apparent calcium lack. This is probably one factor in the need for extra calcium, but further work has indicated that it is probably not the only or even the most important factor.

A similar toxic picture can be produced by the administration of guanidine compounds. Following subcutaneous doses of 250 mgm. of guanidine hydrochloride per kilo body weight, dogs show fibrillary twitching of muscles, tetanic convulsions, gastro-intestinal irritation with bloody vomitus and diarrhea, with usually a period of extreme depression and weakness for some time before death, which occurs 12 to 15 hours after the drug is injected. Four or 5 hours after the guanidine is administered there is a marked fall in blood sugar and the hypoglycemia becomes extreme unless a diet very rich in calcium and carbohydrate has been fed for some time preceding the experiment.