Part 24

February 14: 9 a. m., found dead.

Guinea pig 45. Female. Weight, 435 grams. Diet, oats for about one month previous to injection.

March 17: 3 p. m., 3.5 cc of 2 per cent caffein injected subcutaneously in the back (0.160 gram per kilo); 4.35 p. m., no symptoms; 5.40 p. m., no symptoms.

Guinea pig 39. Male. Weight, 820 grams. Diet, oats and carrots.

February 12: 11 a. m., 6 cc (0.15 gram per kilo) 2 per cent caffein injected subcutaneously in back.

February 14: 9 a. m., alive; seemed to be in good condition; found dead at 1 p. m.

Guinea pig 41. Weight, 660 grams. Diet, oats and carrots one week previous to injection.

February 12: 11 a. m., 5 cc (0.15 gram per kilo) 2 per cent caffein injected subcutaneously.

February 14: 2 p. m., pig alive; apparently normal.

February 18: Guinea pig still alive and apparently in good condition.

Guinea pig 46. Female. Weight, 470 grams. Diet, oats about one month previous to experiment.

March 17: 3.15 p. m., 4 cc (0.170 gram per kilo) 2 per cent caffein injected into back subcutaneously; 4.35 p. m., reflexes increased, tremors on handling marked; 5.40 p. m., no change, symptoms about as before.

March 18: 2.30 p. m., no symptoms.

The experiments of this series (D) likewise showed a considerable difference in the resistance of the individual guinea pigs. Nos. 41, 45, and 46 survived; the rest of the pigs died within 18 hours to 2 days after the administration of caffein. Since an autopsy was held on one only, it is impossible to assign a cause for the variation in the toxicity of caffein in these guinea gigs, as the diet and the other conditions under which the experiments were conducted were the same. It was found in the experiments on cats and rabbits that the presence of morbid processes tends to increase the toxicity of caffein. The observations of Ophüls(66) are of interest in this connection. He found spontaneous lesions of the kidney and liver in a large proportion of guinea pigs examined. The greater susceptibility to caffein of guinea pigs Nos. 39, 40, 49, is probably due therefore to some pathological change which increased its toxicity. About 0.2 to 0.24 gram per kilo may therefore be regarded as the minimum lethal dose for the normal guinea pig when caffein is introduced subcutaneously, the minimum toxic dose being about 150-160 mg per kilo.

Experiments were also conducted to determine the largest dose which does not produce any visible effects. In a number of tests with from 100 to 120 mg caffein per kilo (series E, see Table 6, p. 51) no manifestation of nervous or muscular disturbance nor any departure from the normal in respiratory activity was observed. Such quantities may be regarded as the largest doses which are surely safe for these animals. It is quite possible, therefore, that the greater variation in the toxicity of caffein observed in these experiments is due to morbid conditions. Moreover, there is some evidence that caffein increases the toxicity of certain poisons, as shown by Hale(33) for acetanilid. Is it not possible that caffein may similarly be affected by poisons circulating within the body? Indeed the recent work of Loeb(23) makes this supposition highly probable. This investigator found that caffein and adrenalin injected together produce myocarditis in the rabbit. It is conceivable that the combined action of caffein and some preexisting poison may cause changes which terminate in the death of the animal. The delayed death of guinea pigs after the administration of caffein observed in this and other series may probably be accounted for in this way.

Experiment 57 lends some support to this view. The condition of the kidneys and the presence of a severe gastro-enteritis are sufficient to account for the death of this case. Again the frequent association of gastro-enteritis and congestion of the organs in caffein intoxication found in different animals makes it highly probable that these lesions were caused by caffein.

INJECTION INTO THE PERITONEAL CAVITY.

The experiments were carried out with different doses. All the guinea pigs in this series were kept on a uniform diet, consisting of oats. Most of them were of average size and there were no wide variations in their weights. The experiments of series A with the smallest doses were conducted in March and April; all the other experiments it will be noticed were made in October.

SERIES A.

Guinea pig 41. Weight, 700 grams. Diet, oats.

April 1: 3.30 p. m., 4.5 cc 2 per cent caffein (130 mg per kilo) injected into peritoneal cavity. 5.35 p. m., symptoms present but no tetanus.

April 2: Found dead about 2 p. m., duration of life about 22 hours. Autopsy: Subcutaneous hemorrhage at the point of inoculation; serious exudate on visceral and parietal peritoneum with marked inflammation of peritoneum; portions of intestines showed slight enteritis.

Guinea pig 49. Male. Weight, 370 grams. Diet, oats.

April 1: 3.15 p. m., 2.5 cc 2 per cent caffein (135 mg per kilo) injected into the peritoneal cavity; 5.30 p. m., symptoms present; reflexes increased, but no tetanus. Guinea pig survived.

Guinea pig 47. Female. Weight, 550 grams. Diet, oats since about February 4.

March 17: 3.30 p. m., 3.5 cc 2 per cent caffein (127 mg per kilo) injected into peritoneal cavity; 4.35 p. m., increased irritability present, but not marked; 5.40 p. m., symptoms about the same as before.

March 18: 2.30 p. m., condition good; no symptoms. Survived.

Guinea pig 50. Female. Weight, 290 grams. Diet, oats.