To obtain additional evidence regarding the resistance of the various
races of rabbits to caffein and to ascertain the smallest dose which
is surely fatal to the gray rabbit or Belgian hare was the object of
this series of experiments. The diet in all cases consisted of oats,
which was given ad libitum excepting to rabbit No. 235, which received
carrots for one week previous to the injection of caffein. The doses
administered ranged from 267 to 300 mg per kilo and were administered
to different varieties of adult rabbits.
_Rabbit 253. Brown and black, male. Weight, 1,600 grams. Diet,
oats, November 9 to 12._
November 12: 11.30 a. m., urine from bladder acid, no albumen, no
sugar; 11.35 a. m., 22 cc 2 per cent caffein (275 mg per kilo)
injected subcutaneously; 11.45 a. m., rabbit jumped, off the table,
had convulsions, retraction of head and opisthotonos, general tremors,
anterior extremities stretched out, posterior extremities almost
normal, frequent twitchings; died at 12.15 p. m.
_Rabbit 252. Black, female. Weight, 1,335 grams. Diet, oats, November
9 to 12._
November 12: 11.30 a. m., 18 cc 2 per cent caffein (270 mg per kilo)
injected subcutaneously. Urine obtained from bladder before injection,
acid, no albumen, no sugar, color normal, tremors and great excitement
noticed about 12 noon; 4.30 p. m., when handled, showed unusual
restlessness and excitement followed by convulsions with opisthotonos;
occasional twitching, condition bad. Died 4.35 p. m.
_Rabbit 327. White, female. Weight, 820 grams. Diet, oats, March 8 to
16._
March 16: 11.45 a. m., 12 cc 2 per cent caffein (292 mg per kilo)
injected subcutaneously in the back; 2 p. m., found dead, but was still
warm. _Autopsy_: Hemorrhagic area at point of injection into spinal
muscles; subcutaneous abdominal region exhibited a large area of cheesy
purulent material; liver and spleen were engorged; bladder filled;
intestines normal.
_Rabbit 340. White and brown male. Weight, 1,465 grams. Diet, oats._
March 30: 3.20 p. m., 20 cc of 2 per cent caffein (273 mg per kilo)
injected subcutaneously in back.
March 31: 9 a. m., found dead.
_Rabbit 341. White and brown. Weight, 1,450 grams. Diet, oats._
March 30: 3.20 p. m., 20 cc 2 per cent caffein (270 mg per kilo)
injected subcutaneously in back; 4.40 p. m., found in dying condition,
had convulsions; 4.45 p. m., dead.
_Rabbit 326. White, male. Weight, 1,645 grams. Diet, oats, March 8 to
16._
March 16, 1910: 12 noon, 20 cc 2 per cent caffein (243 mg per kilo)
injected subcutaneously in the back; 2 p. m., tremors marked,
hypersensitive, started to run when put on floor; rabbit was not
handled any more than was required for his removal from and return to
cage.
March 17: 9.30 a. m., tremors still present and marked, otherwise
general condition good; no other symptoms.
March 18: 9.30 a. m., no appetite, tremors still present, general
condition poor; died about 2 p. m.
_Rabbit 235. Belgian hare, male. Weight, 1,870 grams. Diet, carrots,
November 2 to 9._
November 10: 11.05 a. m., 25 cc 2 per cent caffein (267 mg per kilo)
injected subcutaneously; reflexes increased and tremors, but no tetanus
observed; found dead next morning.
_Rabbit 316. Belgian hare, female. Weight, 860 grams. Diet, oats,
March 8 to 16._
March 16, 1910: 11.40 a. m., 12 cc 2 per cent caffein (267 mg per kilo)
injected subcutaneously in the back; 2.15 p. m., reflexes somewhat
increased, but not markedly so; walked when put on floor; gait clumsy
and slow; tremors of head observed; 2.35 p. m., rabbit lying in his
cage, posterior extremities extended and rigid, anterior extremities
flexed, head retracted; is still breathing; occasional spasms observed.
Rabbit died at 3 p. m. _Autopsy_: No lesion at point of injection in
dorsal spinal muscles; liver and spleen engorged; intestines injected;
other organs apparently normal.
_Rabbit 395. Belgian hare, male. Weight, 1,410 grams._
August 18: 1 p. m., 20 cc 2 per cent caffein (283 mg per kilo) injected
subcutaneously in the back; 4 p. m., reflexes markedly increased;
5 p. m., reflexes about the same, but no tetanus.
August 19, 9.15 a. m.: Reflexes increased markedly.
August 21, weight, 1,215 grams. Given 275 mg per kilo of caffein; no
symptoms observed.
August 23, found dead. _Autopsy_: Liver greatly engorged; stomach
fairly well distended and mucous membrane in a slightly inflammatory
condition; contents of small intestine liquid in nature, but walls of
same appeared normal; other organs normal in appearance.
_Rabbit 396. Belgian hare, female. Weight, 1,475 grams. Diet, oats._
August 18: 1 p. m., 20 cc 2 per cent caffein (272 mg per kilo) injected
subcutaneously in the back; 4 p. m., reflexes increased markedly;
5 p. m., reflexes increased markedly but no tetanus.
August 19: 10.30 a. m., reflexes still increased very markedly; rabbit
jumps when touched.
August 21: Weight, 1,245 grams. Injected subcutaneously 275 mg of
caffein per kilo; reflexes increased, posterior extremities stiff over
hour later.
August 22: 9 a. m., found dead. _Autopsy_: Thoracic organs normal in
appearance; stomach distended and mucous membrane affected with a
catarrhal inflammation; contents of stomach were covered with a shiny
mucus; contents of small intestine liquid in nature and bile stained;
liver showed a coccidial infestation; kidneys and spleen normal in
appearance.
_Rabbit 397. Belgian hare, male. Weight, 1,375 grams. Diet, oats._
August 19: 10.30 a. m., 20 cc 2 per cent caffein (290 mg per kilo)
injected subcutaneously in the back.
August 22: 9 a. m., found dead. _Autopsy_: Stomach distended with
ingesta; mucous membrane exhibited a catarrhal inflammation with
excessive secretions; major portion of intestines showed a condition
similar to that of stomach, contents consisting mainly of a shiny
mucus; liver enlarged; other organs apparently normal.
_Rabbit 398, Belgian hare, female. Weight, 1,570 grams. Diet, oats._
August 19: 10.30 a. m., 23 cc 2 per cent caffein (293 mg per kilo)
injected subcutaneously in the back; 4 p. m., found dead. _Autopsy_:
Thoracic organs seemingly normal; mucous membrane of stomach exhibited
a catarrhal inflammation generally; large intestines somewhat impacted
but walls appeared normal; other organs normal.
_Rabbit 399, Belgian hare, male. Weight, 1,725 grams. Diet, oats._
August 19: 10.30 a. m., 26 cc 2 per cent caffein (300 mg per kilo)
injected subcutaneously in the back; found dead at 4.30 p. m.
_Autopsy_: Lungs slightly congested; liver engorged and friable; gall
cyst well filled; stomach exhibited catarrhal gastritis; injection of
mesenteries and intestines; kidney showed marked cortical congestion.
The results of the experiments of this series likewise indicate that
the Belgian hare is more resistant to caffein than the rabbits of other
varieties. Thus, of the four gray rabbits (Nos. 235, 316, 395, and
396), which received 267 to 283 mg of caffein per kilo, two died and
two lived,[B] one of which, 396, showed the presence of coccidiosis of
the liver. On the other hand it will be observed that the black and
white rabbits which received from 270 to 275 mg of caffein per kilo all
died from the effects of the drug; one within 1 hour and 25 minutes
and another within 50 hours after the administration of the caffein,
while No. 340 died in the night. Furthermore it will be noted that of
the last three rabbits of this series, which were Belgian hares and
received 290, 293, and 300 mg of caffein, two died six hours after the
injection, while the other, No. 397, lived three days. The minimum
fatal dose of caffein for Belgian hares is, therefore, about 290 to 300
mg per kilo when injected subcutaneously, which is about 50 per cent
greater than for rabbits of other varieties.
[B] Survived first dose.