Part 9

March 18: 3.30 p. m., 4 cc 2 per cent caffein (103 mg per kilo) injected into subcutaneous tissues in the back; 5.30 p. m., no symptoms.

March 19: 9 a. m., no symptoms.

March 25: Rabbit alive in good condition; weight, 825 grams.

Rabbit 320. Black, male. Weight, 1,040 grams. Diet, oats.

March 17: 11 a. m., 6 cc 2 per cent caffein (115 mg per kilo) injected subcutaneously in the back; only a few drops of urine obtained from bladder before injecting caffein; 1 p. m., rabbit very restless; ran away when placed on floor; cried when touched with a piece of paper; no tremors observed, but rabbit became exhausted and was unable to walk; legs extended out; after running for about a minute dyspnoea was very marked, but rabbit soon raised himself on his legs; 5.40 p. m., rabbit up on his legs.

March 18: 9 a. m., found dead, but still warm. Autopsy: Lungs studded with small grayish white nodules, adhesions to costal pleura; probably lesions of coccidiosis; liver studded with coccidiosis nodules. Hemorrhages at point of inoculation.

Rabbit, 551. Gray, female. Weight, January 26, 1,650 grams. Diet, oats; fed 20 cc of 25 per cent alcohol daily from January 26-31.

January 31: Weight, 1,450 grams; 10.20 a. m., temperature 101.6°; 10.45, a. m., temperature 101.6°; received 7 cc 2 per cent caffein subcutaneously into back; 11.15 a. m., convulsions of short duration; raised himself on posterior legs, anterior legs wide apart; 4.10 p. m., looked normal, not hypersensitive; 4.30 p. m., condition seemed to be good.

February 1: 9 a. m., found dead, was alive at 5.30 p. m. of previous day. Autopsy: Lesions found involved thoracic cavity mainly; lungs were hepatized and a fibro plastic exudate caused them to adhere to costal pleura; liver engorged and appeared fatty; no marked lesions affecting digestive tract, a slight catarrh of stomach being the only noticeable feature; kidneys and spleen normal.

TABLE 1.--Subcutaneous injections of caffein--rabbits.

SERIES A.

----+--------+-------+-------------+--------------+-------+----------- | |Caffein| Appearance | Duration | | No.| Weight.| per | of symptoms | of life. | Diet. | Remarks. | | kilo | in-- | | | ----+--------+-------+-------------+--------------+-------+----------- |Grams.| Mg. | | | | 332| 1,070 | 158 |1 hour |Survived | Oats |Gray. | | | 45 minutes| | | 331| 1,170 | 153 | do. | do. | do. | Do. 328| 1,200 | 150 | do. | do. | do. | Do. 322| 1,065 | 150 |1 hour | do. | do. |White. 217| 1,355 | 147 | | do. | do. | Do. 219| 1,820 | 153 | | do. | do. |Maltese. 194| 1,490 | 174 | | do. | do. |White. 191| 1,915 | 167 | | do. | do. |Light brown. ----+--------+-------+-------------+--------------+-------+------------

SERIES B, GROUP I.

----+--------+-------+-------------+--------------+-------+------------- 95| 1,478 | 210 |2 hours |3 hours |Oats |White. | | | 50 minutes | 10 minutes | | 96| 1,585 | 200 |1 hour |About 18 hours| do. |Gray white. 112| 875 | 205 |30 minutes | do. | do. |Black. 119| 1,060 | 188 | | do. | do. |Yellow white. 195| 1,300 | 200 | |3 hours |Carrots|White. | | | | 10 minutes | | 208| 1,068 | 188 |2 hours |About 24 hours| do. |Gray. ----+--------+-------+-------------+--------------+-------+-------------

SERIES B, GROUP II.

----+--------+-------+-------------+--------------+-------+----------- 247| 1,295 | 200 |2.5 hours |Survived |Oats |Gray. 248| 1,305 | 200 |3 hours | do. | do. | Do. 337| 1,040 | 211 |1.5 hours | do. |Carrots| Do. 336| 1,045 | 211 | do. | do. | do. | Do. ----+--------+-------+-------------+--------------+-------+-----------

SERIES C.

----+--------+-------+-------------+--------------+-------+------------ 122| 2,060 | 250 |2 hours |1.5 days |Oats |White. | | | 55 minutes | | | 234| 1,650 | 242 | |About 24 hours|Carrots| Do. 335| 1,170 | 240 |1 hour | do. | do. |Gray | | | | | |coccidiosis. 249| 1,185 | 236 |4 hours |Survived |Oats |Gray. 321| 1,135 | 246 |2 hours | do. | do. |Yellow. | | | 10 minutes | | | 250| 1,435 | 252 |4 hours | do. | do. |Gray. | | | 35 minutes | | | 334| 1,270 | 240 |1 hour | do. |Carrots| Do. 233| 1,675 | 238 |6 hours |26 hours | do. |White. | | | 10 minutes | | | ----+--------+-------+-------------+--------------+-------+------------

SERIES D.

----+--------+-------+-------------+--------------+-------+----------- 253| 1,600 | 275 |10 minutes |35 minutes |Oats |Brown and | | | | | | black. 252| 1,335 | 270 |30 minutes |4 hours | do. |Black. | | | | 55 minutes | | 327| 820 | 292 | |2 hours | do. |White. | | | | 15 minutes | | 340| 1,465 | 273 | |About 18 hours| do. |White and | | | | | | brown. 341| 1,450 | 270 | |1 hour | do. | Do. | | | | 25 minutes | | 326| 1,645 | 243 |2 hours |50 hours | do. |White. 235| 1,875 | 267 | |20 hours |Carrots|Gray. 316| 860 | 267 |2 hours |3 hours |Oats | Do. | | | 45 minutes | 20 minutes | | 395| 1,410 | 283 |3 hours |Survived | | Do. 395| 1,215 | 275 | do. |About 2 days |Oats | Do. 396| 1,475 | 272 | do. |Survived | do. | Do. 396| 1,245 | 275 |1 hour |About 18 hours| do. | Do. 397| 1,375 | 290 | |3 days | do. | Do. 398| 1,570 | 293 | |5.5 hours | do. | Do. 399| 1,725 | 300 | |6 hours | do. | Do. ----+--------+-------+-------------+--------------+-------+-----------

SERIES E.

----+--------+-------+-------------+--------------+-------+------------ 325| 1,065 | 112 |2 hours |Less than | Oats |White female. | | | | 22 hours | | 330| 935 | 107 |None |Survived | |Gray. 329| 775 | 103 |do. | do. | |Gray male. 320| 1,040 | 115 |2 hours |46 hours | Oats |Black male. 551| 1,450 | 100 |30 minutes |Less than | do. |Gray female. | | | | 24 hours | | ----+--------+-------+-------------+--------------+-------+------------

ADMINISTRATION BY MOUTH.

These experiments were carried out on two varieties of rabbits, the white and the gray. The diet consisted chiefly of oats, but in a few cases carrots formed the exclusive diet. Food and water were given ad libitum. A 2 per cent solution of caffein was administered through a stomach tube. Since the resistance to most drugs is commonly supposed to be greater when given by mouth than when administered by any other path, doses of 175 to 200 mg per kilo were fed in a series of preliminary experiments, all of which were performed on gray rabbits weighing from 865 to 1,135 grams, and which were fed carrots for several days previous to the experiment. Three of the rabbits survived, two without showing any symptoms; in the other case paralysis of the posterior extremities was observed five hours after he received caffein and he was found dead the next morning. Unfortunately no autopsy was performed. The low resistance to caffein of this animal was probably due to some abnormal condition which developed about the time of the experiment, since this rabbit received 325 mg of caffein per kilo two weeks previously and increased reflexes only were observed as a result of this treatment. Hence 200 mg of caffein per kilo can not be considered the toxic dose when fed by mouth. In the following experiments larger doses were therefore given.

SERIES A.

Rabbit 248. Belgian hare. Weight, 1,170 grams. Diet, oats.

November 17: 1.20 p. m., 19.5 cc 2 per cent caffein (330 mg per kilo) administered by the mouth; 4.30 p. m., somewhat hypersensitive.

November 19: No symptoms; at 9 a. m., urine collected, no reduction of Fehling's solution; rabbit survived.