Part 6

Although symptoms appeared in rabbits of Group I (see table, page 25) about the same time after the administration of caffein as in the rabbits of the preceding series all of them terminated fatally 2¼ hours to 24 hours after its administration. Two of these rabbits (Nos. 195 and 208) were fed carrots for several days before the injection of caffein, the others were fed oats. Since symptoms and death appeared in these two rabbits about the same time as in the rest of this group it may be concluded that caffein is not less toxic when carrots are fed than when oats form the exclusive diet. But since rabbit No. 208 was poorly nourished and ulceration of the rectum was observed in No. 195 it is quite possible that caffein might be less toxic in normal rabbits on this diet. This was tested in rabbits Nos. 336 and 337, both of which seemed to be free from abnormality and were well nourished. Since these rabbits survived and manifested mild symptoms only of intoxication it would seem that a carrot diet decreases the toxicity of caffein.

It was suggested, however, that another factor might be the cause of the greater resistance to caffein in these two rabbits, namely, race. This was tested in rabbits 247 and 248, both Belgian hares. Since the toxicity of caffein in these two rabbits was the same as in Nos. 336 and 337, diet as a factor in acute caffein intoxication may be disregarded. The greater resistance to caffein of these four rabbits is in all probability due, therefore, to a difference of race. This suggestion gained additional support from the experiments of the next series.

SERIES C.

The object of these experiments was to determine the minimum fatal dose for the gray rabbit and to obtain additional evidence as to the toxicity of caffein in the several varieties of rabbits. Eight experiments were performed, in which from 236 to 252 mg per kilo were given. The white rabbits, three in number, received 250, 242, and 238 mg per kilo. All the others (which were Belgian hares) received from 236 to 252 mg per kilo. Two of the white rabbits were fed carrots for one week preceding the injection of caffein. The other was fed oats. Three of the Belgian hares were on a diet of oats, two were fed carrots the week before the experiment with caffein.

Rabbit 122. White, female. Weight, 2,060 grams. Diet, oats.

April 14: 25 cc of 2 per cent caffein (250 mg per kilo) in aqueous solution injected subcutaneously in the back at 1.35 p. m.; 4.30 p. m., tremors, reflexes increased, condition otherwise good.

April 16: 9 a. m., found dead in cage. Autopsy: Liver deeply congested; kidneys congested in cortex and medulla; stomach showed small hemorrhagic areas, perforating ulcers in pyloric portion; small intestine petechiated on mucosa; lungs and spleen normal.

Rabbit 234. White, female. Weight, 1,650 grams. Diet, November 2-9, carrots.

November 9: 10.45 a. m., 20 cc 2 per cent caffein (242 mg per kilo) administered subcutaneously.

November 10: 9 p. m., found dead.

Rabbit 335. Gray hare, female. Weight, 1,170 grams. Diet, March 31 to April 7, carrots.

April 7: 9.30 a. m., 14 cc 2 per cent caffein solution (240 mg per kilo) injected subcutaneously in the back; 10.30, reflexes much increased, rabbit is extremely sensitive.

April 8: 9 a. m., found dead. Autopsy: Liver was congested and contained several coccidiosis nodules; stomach distended with rather dry food mass; mucosa exhibited mild catarrhal inflammation; mucosa of intestines also slightly inflamed.

Rabbit 249. Belgian hare, female. Weight, 1,185 grams. Diet, oats.

November 11: Urine, 5 cc, from bladder acid to litmus, no sugar, no albumin; 11.50 a. m., 14 cc 2 per cent caffein (236 mg per kilo) administered subcutaneously; 3.45 p. m., reflexes increased, hyperæsthesia marked, but no tetanus, even when handled; 30 cc urine collected at 4 p. m., reduction of Fehling's solution considerable.

November 12: 10 a. m., 8 cc urine collected, reduction heavy, only a few cubic centimeters obtained from bladder, did not contain any sugar, general condition of rabbit good, no symptom of caffein intoxication.

Rabbit 321. Yellow, female. Weight, 1,135 grams. Diet, oats.

March 16, 1910: 11.50 a. m., 14 cc 2 per cent caffein (246 mg per kilo) injected subcutaneously in the back; 2 p. m., reflexes increased, is very sensitive, started to run when put on floor, no handling except what was required for removal and return to cage, feces soft.

March 17: 9.30 a. m., condition good, rabbit put on floor, gait normal, but does not care to walk.

March 18: 9 a. m., walks around when put on floor, appetite good, condition seems to be normal.

March 25: 11 a. m., rabbit still alive, condition good.

Rabbit 250. Belgian hare, female. Weight, 1,435 grams. Diet, oats at least two days before the experiment.

November 11: 11 a. m., urine obtained from bladder acid to litmus, no albumin, no sugar; 11.10 a. m., 18 cc, 2 per cent caffein (252 mg per kilo); 3.45 p. m., reflexes and hyperæsthesia, no tetanus; 4 p. m., 60 cc urine, marked reduction of Fehling's solution.

November 12: 10 a. m., condition of rabbit good, no symptoms of caffein intoxication, 80 cc urine collected, sugar considerable, only a few cubic centimeters of urine obtained from bladder, no reduction of Fehling's solution.

Rabbit 834. Belgian hare, female. Weight, 1,270 grams. Diet, carrots, March 31 to April 7.

April 7: 9.30 a. m., 15 cc 2 per cent caffein (240 mg per kilo) injected subcutaneously in the back; 10.30 a. m., reflexes much increased, rabbit extremely sensitive.

April 8: 9 a. m., condition good, no symptoms.

Rabbit 233. White, male. Weight, 1,675 grams. Diet, carrots, November 2 to 9.