Part 37

SERIES C.

The subjects used in these experiments were rabbits of medium size and were apparently young or at any rate were not very old. The series was planned for the study of the possible effect of diet on the toxicity of caffein when given for some time, and therefore oats were substituted for carrots, which had been fed in the previous work, as already stated. Caffein was given by mouth in the usual way, in 1 per cent solution, 100 mg. per kilo daily. Fourteen rabbits were used for these tests. Their weights were recorded daily and observations made at frequent intervals during the day.

The only change noticed in all of the experiments of this series was progressive loss of weight which set in from 3 to 8 days after the administration of the drug was begun. The duration of life varied considerably. No. 382 died after the first dose. No. 389 lived 2 days, No. 386, 3 days, and No. 385, 5 days; No. 390 lived 7 days and No. 404 lived 20 days after the administration of caffein was begun. The duration of life in all the others was from 11 to 16 days. The findings at autopsy are interesting and suggestive as regards the possible explanation of the effects of repeated dosage of caffein. In eight of the rabbits there was involvement of the mucous membrane of the stomach or intestines or of both. Since the same condition of the gastro-intestinal canal was observed in previous experiments with caffein when injected subcutaneously, the mere passing of the tube into the stomach is obviously not the cause of this condition. The fatal outcome due is therefore, as was suggested above, to inanition brought about by the condition of the gastro-intestinal canal. Moreover parallel experiments carried out on rabbits in the same way with alcohol survived this treatment much longer. Obviously then the passing of the soft rubber catheter is not the cause of this condition of the gastro-intestinal canal nor the diet. Rabbits were fed oats exclusively for several months in this laboratory and thrived. The presence of pneumonia in the other rabbits of this series may be regarded as accidental, as it is inconceivable that one or two doses of caffein, as was the case in Nos. 382 and 389, could predispose the lungs to infection. The results of these experiments therefore are in harmony with those of the preceding two series, indicating that caffein does not accumulate in the body, and that the toxicity of caffein, whether of the single dose or of repeated doses is the same, on a diet of carrots or of oats. These results also show that caffein is much more toxic with repeated dosage. As stated in the historical part of this bulletin the same view was held by Gourewitch.(28)

Rabbit 386. Belgian female.

Given 1 cc of 1 per cent caffein for each 100 grams, through stomach tube.

--------+--------+---------- Date. | Weight.|Treatment. --------+--------+---------- |Grams.| cc. Aug. 17| 1,300 | 13.0 Aug. 18| 1,215 | 12.0 Aug. 19| (?) | (?) --------+--------+----------

August 20: Found dead 9 a. m. Autopsy: Lungs slightly congested; liver engorged and friable; gall cyst well filled.

Rabbit 389. Black male.

Given 1 cc of 1 per cent caffein for each 100 grams, through stomach tube.

--------+--------+---------- Date. | Weight.|Treatment. --------+--------+---------- |Grams.| cc. Aug. 17| 1,070 | 10.0 Aug. 18| 1,025 | 10.0 --------+--------+----------

August 19: Found dead 9 a. m. Autopsy: Lungs severely congested and partially hepatized; liver was engorged; other organs appeared normal.

Rabbit 382. Belgian female.

On August 17 weighed 1,035 grams; received 1 cc of 1 per cent caffein for each 100 grams; 10 cc of 1 per cent caffein given in all.

August 18: Found dead 9 a. m. Autopsy: Lungs congested and hepatized; liver engorged; stomach showed numerous petechial hemorrhages on mucosa; kidneys slightly congested; intestines appeared normal.

Rabbit 385. Belgian female.

Given 1 cc of 1 per cent caffein for each 100 grams, through stomach tube.

--------+--------+---------- Date. | Weight.|Treatment. --------+--------+---------- |Grams.| cc. Aug. 17| 780 | 8.0 Aug. 18| 760 | 7.5 Aug. 19| 755 | 7.5 Aug. 20| 715 | 7.0 Aug. 21| 700 | 7.0 --------+--------+----------

August 22: Found dead 9 a. m. Autopsy: Lungs exhibited pneumonic lesions, with inflammation of adjacent pleura; a fibro-plastic exudate present around lung; liver showed a coccidial infestation; stomach distended with ingesta; mucous membrane characterized by a catarrhal inflammation; contents of small intestine liquid in nature and bile stained; large intestine somewhat impacted; liver and kidneys seemingly normal.

Rabbit 404. White male.

Given 1 cc 1 per cent caffein for each 100 grams.

------------+---------+------------ Date. | Weight. | Treatment. ------------+---------+------------ |Grams. | cc. Aug. 20 | 1,465 | 14.5 Aug. 21 | 1,475 | 14.5 Aug. 22(1) | | Aug. 23 | 1,475 | 14.5 Aug. 24 | 1,400 | 14.0 Aug. 25(2) | 1,405 | 14.0 Aug. 26 | 1,415 | 14.0 Aug. 27 | 1,400 | 14.0 Aug. 28(1) | | Aug. 29 | 1,310 | 13.0 Aug. 30 | 1,320 | 13.0 Aug. 31 | 1,330 | 13.5 Sept. 1 | 1,335 | 13.5 Sept. 2 | 1,315 | 13.0 Sept. 3 | 1,350 | 13.5 Sept. 4 | 1,335 | 13.5 Sept. 5 | 1,350 | 13.5 Sept. 6 | 1,380 | 14.0 Sept. 7 | 1,375 | 14.0 Sept. 8 | 1,325 | 13.0 ------------+---------+------------

(1) Not fed.

(2) Reflexes.

September 9: Found dead 9 a. m. Autopsy: Both lungs showed extensive pneumonia, with adhesions to pleura; pleuritis and pericarditis very marked; large amount of fibrous exudate in pleural cavity; pyloric end of stomach slightly congested; liver congested; other organs normal.

Rabbit 393. Belgian.

Given 1 cc of 1 per cent caffein to each 100 grams, through stomach tube.

------------+---------+------------ Date. | Weight. | Treatment. ------------+---------+------------ | Grams.| cc. Aug. 17 | 950 | 9.5 Aug. 18 | 910 | 9.0 Aug. 19 | 895 | 9.0 Aug. 20 | 910 | 9.0 Aug. 21 | 905 | 9.0 Aug. 22(1) | | Aug. 23 | 825 | 8.0 Aug. 24 | 870 | 8.5 Aug. 25 | 835 | 8.5 Aug. 26 | 780 | 8.0 Aug. 27 | 765 | 7.5 Aug. 28(1) | | Aug. 29 | 710 | Aug. 30(2) | | Aug. 31(1) | | ------------+---------+------------

(1) Not fed.