Part 26

Guinea pig 63. Gray and white male. Weight, 340 grams. Diet, oats.

October 5: 11.20 a. m., 4 cc of 2 per cent caffein (235 mg per kilo) injected into peritoneal cavity.

October 14: Alive and in good condition.

Guinea pig 64. Brown and black female. Weight, 305 grams.

October 5: 11.35 a. m., 3.8 cc 2 per cent solution caffein (250 mg per kilo) injected into peritoneal cavity; 11.40 a. m., tetanus--survived, convulsions off and on, died at 4.15 p. m. Autopsy: Findings exactly the same as in No. 67.

Examination of the results of the experiments by intraperitoneal injections showed that 0.2 gram caffein per kilo was toxic in two guinea pigs (Nos. 59 and 58). Severe symptoms were observed within 15 minutes in No. 56 and within one hour in No. 55 after the administration of approximately the same dose of caffein. One of these died within three and one-half hours; the other, No. 56, made a good recovery from the acute effects. This amount of caffein may be regarded, therefore, as the minimum toxic dose for the guinea pig when injected into the peritoneal cavity. This is corroborated by the experiments of series B in which smaller doses failed to show any muscular, nervous, or respiratory symptoms, nor were there any after effects noticed, as all of them survived and were kept under observation for some time. The guinea pigs of series A, however, seem to contradict these results. It will be remarked that appreciably smaller doses induced symptoms in all of them, and one case terminated fatally. The seasonal variation, as already pointed out, is in all probability likewise responsible for the difference in the resistance between the guinea pigs of series A and B. Tests were made also to determine the minimum fatal dose. For this purpose the experiments of series D were performed. The resistance of No. 63 in this series is quite striking. We are unable to explain such a discrepancy in the results obtained under practically uniform conditions. The minimum fatal dose of caffein, when injected into the peritoneal cavity, is therefore about 240 to 250 milligrams per kilo. These amounts, it will be observed, were rapidly fatal, in striking contrast to the results obtained when such doses were injected subcutaneously. This is probably due to a better absorption from the peritoneal cavity than from the subcutaneous tissues.

ADMINISTRATION BY MOUTH.

All the guinea pigs in these experiments were kept on a diet of hay and oats and were of large size. The tests were made with different doses of caffein in order to determine the limits of toxicity when the drug was administered by mouth.

Guinea pig 129. White and black male. Weight, 855 grams. Diet, oats and hay.

June 6: 2.20 p. m., 12 cc of 2 per cent caffein (0.28 gram per kilo) by mouth; 3 p. m., reflexes increased; 5 p. m., reflexes still more increased; no other symptoms.

June 7: 9 a. m., found dead; guinea pig passed 75 cc urine, which was almost colorless. Autopsy: Heart and blood vessels injected; lungs congested; small intestines congested; other organs apparently normal.

Guinea pig 130. Black and brown male. Weight, 800 grams. Diet, oats and hay.

June 6: 2.30 p. m., 12 cc of 2 per cent caffein (0.3 gram per kilo) administered by mouth; 3 p. m., reflexes increased; 5 p. m., increase of reflexes greater than at 3 p. m.

June 7: 9 a. m., found dead; only a few cubic centimeters of urine passed since 4 p. m. Autopsy: Heart and blood vessels injected; lungs congested; small intestines congested slightly.

Guinea pig 181. White and yellow male. Weight, 860 grams. Diet, oats and hay.

June 6: 2.40 p. m., 12 cc 2 per cent caffein administered by mouth; 3 p. m., reflexes increased; 5 p. m., reflexes still more marked.

June 7: 9 a. m., found dead, pig passed about 5 cc urine since 4 p. m. of previous day. Autopsy: Same as in No. 130.

Guinea pig 136. White and black male. Weight, 1,000 grams. Diet, oats and hay.

June 9: 4 p. m., 7.5 cc 2 per cent caffein solution injected subcutaneously into the back; 4.50 p. m., reflexes increased.

June 10: 9.30 a. m., more sensitive than normal guinea pigs, but reflexes not quite so marked as at 5 p. m. previous day, about 15 cc urine passed since caffein was injected, reduction of Fehling's solution considerable, no albumin.

June 13: Alive and in good condition. Appetite good. (NOTE.--Parallel test with urine from two guinea pigs which did not receive caffein failed to show reduction of Fehling's solution.)

Guinea pig 137. White and brown male. Weight, 925 grams. Diet, oats and hay.

June 9: 4 p. m., 7 cc 2 per cent solution caffein injected subcutaneously; 4.50 p. m., reflexes increased.

June 10: Reflexes less marked than at 5 p. m. previous day, but is more sensitive than normal guinea pig, about 10 cc urine passed since injection of caffein, moderate amount of reduction of Fehling's solution.

June 13: Guinea pig alive, appetite good, condition good.

June 16: 9 a. m., found dead.

Guinea pig 135. White and black male. Weight, 955 grams. Diet, hay and oats.

June 9: 3 p. m., 7.5 cc 2 per cent caffein solution given by mouth through stomach tube; 4.50 p. m., reflexes increased.