Part 17

February 14: 3 p. m. 14 cc 2 per cent caffein injected into the gluteal muscles of the right side; 3.10 p. m., restless, jumped off the table and walked about, reflexes increased; 3.45 p. m., passed 30 cc clear, straw-colored urine; 4.45 p. m., allowed to walk about, ran across the room, about 20 feet, looked tired, stretched himself out on the floor, then raised himself and walked about showing no disturbance of gait.

February 15: 9 a. m., found dead.

Rabbit 578. Gray, female. Weight, 1,670 grams.

February 14: 3.05 p. m., 18 cc 2 per cent caffein solution injected into the gluteal muscles of the right side; 3.15 reflexes increased, but not restless; 5 p. m., allowed to walk about, no symptoms observed.

February 15: Found dead.

Rabbit 579. White and gray, male. Weight, 1,490 grams.

February 14: 3.15 p. m., 15 cc 2 per cent caffein solution injected into the gluteal muscles of the right side; put in cage; 3.30 p. m., reflexes increased; 5 p. m., taken out of cage and allowed to walk across the room, no special symptoms noticed.

February 23: Still alive.

Rabbit 580. Gray male. Weight, 1,510 grams.

February 14: 3.35 p. m., 15 cc 2 per cent caffein solution injected into lumbar muscles.

February 23: Still alive, in good condition.

Rabbit 581. Gray female. Weight, 1,680 grams.

February 14: 3.45 p. m., 17 cc 2 per cent caffein solution injected into the lumbar muscles of the right side; 4 p. m., reflexes increased; 4.15 p. m., jumped off the table and had wild convulsions, became very restless, walked about the laboratory; 4.25 p. m., had convulsions occasionally; 4.30 p. m., extremities extended and quite rigid; 4.35 p. m., convulsions and death.

Rabbit 582. Gray male. Weight, 1,870 grams.

February 14: 4.15 p. m., 18 cc 2 per cent caffein solution injected into the lumbar muscles of right side; 5 p. m., reflexes increased; walked about in the room, then rested; 5.15 p. m., had short spasm when handled.

February 23: Alive; good condition.

The data presented in these experiments show that the toxicity of caffein when injected into the muscles of the lumbar regions is the same as when injected into the gluteal muscles. The rabbits of series A received approximately 0.2 gram caffein per kilo and two died as a result of this treatment. The other two survived but symptoms of caffein intoxication were observed.

In series B smaller doses proved fatal, from which it would appear that caffein is more toxic when injected into the lumbar muscles. Further observations, however, failed to corroborate the results obtained in this series. Thus, in series C, 130 to 150 mg of caffein per kilo injected into the lumbar muscles produced mild symptoms only. Experiments with larger doses showed that 0.180 gram caffein per kilo may cause death. It will be noticed, on the other hand, that rabbit No. 455 survived a dose of 0.2 gram per kilo. New experiments were therefore carried out in which the same amounts of caffein in proportion to the weight of the animals were injected into the lumbar muscles as into the gluteal muscles. As shown in the experiments of series D, one rabbit (No. 581) died shortly after caffein was injected into the lumbar muscles; two recovered. Two of the three which received injections into the gluteal muscles were found dead the next day; one recovered. Post-mortem examination failed to indicate the presence of any abnormalities. The rate of absorption of caffein from the gluteal and from the lumbar muscles seems to be, therefore, the same, or not to differ very much. The observations of Auer and Meltzer(7) are of interest in this connection. According to their investigations adrenalin is more rapidly absorbed from the lumbar than from the gluteal muscles. This is in all probability due to the greater delicacy of the test they employed (since they judged the rate of absorption by the effect of adrenalin on blood pressure) as well as to the much greater activity of the substance.

TABLE 4.--Intramuscular injections.

SERIES A.

----+--------+-------+----------+-----------+----------+-------------- | |Caffein| | | | No.| Weight.| per | Symptoms | Duration | Site of | Remarks. | | kilo | after-- | of life. |injection.| ----+--------+-------+----------+-----------+----------+-------------- |Grams.|Gram.| | | | 284| 1,100 | 0.200 | 3 hours |Less than | Gluteal |White and | | | | 20 hours | | brown female. 286| 1,315 | .1977| 2 hours |Survived | do. |White and | | | | | | black female. 285| 1,385 | .200 | Present | do. | do. |Yellow and | | | | | | white female. 287| 1,140 | .210 |15 minutes|25 minutes | do. |Gray female. ----+--------+-------+----------+-----------+----------+--------------

SERIES B.

----+--------+-------+----------+-----------+----------+------------- 307| 1,175 | 0.136 | 5 hours |6 hours, | Lumbar |Gray female. | | | | 20 minutes| | 306| 1,860 | .134 | 3 hours |4 hours | do. | Do. 181| 1,230 | .130 | 4 hours |5 hours | do. |Gray. ----+--------+-------+----------+-----------+----------+-------------

SERIES C.

----+--------+-------+----------+-----------+----------+------------- 425| 1,520 | 0.131 | 1 hour |Survived | Lumbar |Gray. 426| 1,405 | .142 |30 minutes| do. | do. |Gray female. 427| 1,830 | .153 |50 minutes| do. | do. | Do. 453| 1,160 | .200 |30 minutes|Less than | do. |Gray male. | | | | 20 hours | | 455| 1,185 | .200 | do. |Survived | do. |Gray female. 428| 1,650 | .180 | |Less than | do. |Gray male. | | | | 20 hours | | 429| 1,340 | .200 | | do. | do. | Do. ----+--------+-------+----------+-----------+----------+-------------

SERIES D. ----+--------+-------+----------+-----------+----------+------------- 577| 1,380 | 0.200 |10 minutes|Less than | Gluteal |Gray male. | | | | 18 hours | | 578| 1,670 | .210 | do. | do. | do. | Do. 579| 1,490 | .200 |15 minutes|Survived | do. |White and | | | | | | gray male. 580| 1,510 | .200 | | do. | Lumbar |Gray male. 581| 1,680 | .200 |15 minutes|50 minutes | do. | Do. 582| 1,870 | .192 |45 minutes|Survived | do. | Do. ----+--------+-------+----------+-----------+----------+-------------

Examination of Table 4 shows that 14 rabbits received from 180 to 210 mg caffein per kilo. The appearance of symptoms in these rabbits varied considerably. In some increased reflexes could be noticed in 10 to 15 minutes after the injection of caffein; in others it was delayed 2 or 3 hours. It might be added that the onset of symptoms occurred in many cases very soon after the administration of the drug--on an average about 10 to 30 minutes after the drug was injected. After smaller doses were administered by injection into the lumbar muscles the appearance of symptoms was delayed several hours in some cases. The duration of life in these 14 rabbits varied considerably. Eight of them died within 1 to 20 hours; six survived. About 0.2 gram caffein per kilo may be regarded as the minimum fatal dose, while the minimum toxic dose is somewhere between 130 and 150 mg per kilo.

INTRAVENOUS INJECTION.