Part 28

TABLE 7.--Injection into peritoneal cavity; guinea pigs.

SERIES A.

------+--------+-------+----------+----------+--------+------+-------- Number| |Caffein|Appearance| Duration | | | of pig|Weight. | per | of | of | Diet. |Month.|Remarks. | | kilo. | symptoms.| life | | | ------+--------+-------+----------+----------+--------+------+-------- |Grams.|Gram.| | | | | 41 | 700 | 0.130 |2 hours |22 hours |Oats |April |Male. 49 | 370 | .135 |2 hours |Survived | do. | do. | Do. | | |15 minutes| | | | 47 | 550 | .127 |1 hour | do. | do. |March |Female. 50 | 290 | .138 |2 hours | do. | do. |April | Do. ------+--------+-------+----------+----------+--------+------+--------

SERIES B.

------+--------+-------+----------+----------+-------+-------+------- 51 | 415 | 0.144 | None |Survived |Oats |October|Female. 52 | 450 | .155 | do. | do. | do. | do. |Male. 53 | 490 | .163 | do. | do. | do. | do. | Do. ------+--------+-------+----------+----------+-------+-------+-------

SERIES C.

------+--------+-------+----------+----------+-------+-------+-------- 59 | 375 | 0.200 |15 minutes|Survived |Oats |October|Gray and | | | | | | | white. 58 | 380 | .200 |10 minutes| do. | do. | do. | 56 | 440 | .200 |15 minutes|14 days | do. | do. |Male. 55 | 690 | .188 | 1 hour |3 hours | do. | do. | Do. | | | |30 minutes| | | ------+--------+-------+----------+----------+-------+-------+--------

SERIES D.

------+--------+-------+----------+----------+-------+-------+-------- 67 | 330 | 0.240 |5 minutes |30 minutes|Oats |October|Male. 63 | 340 | .235 | |Survived | do. | do. | Do. 64 | 305 | .250 |25 minutes|4 hours | do. | do. |Female. | | | |40 minutes| | | ------+--------+-------+----------+----------+-------+-------+--------

TABLE 8.--Caffein by mouth; guinea pigs.

SERIES J.

------+--------+-------+----------+----------+-------+-------+-------- Number| |Caffein|Appearance| Duration | | | of pig|Weight. | per | of | of | Diet. | Month.|Remarks. | | kilo. | symptoms.| life | | | ------+--------+-------+----------+----------+-------+-------+-------- |Grams.|Gram.| | | | | 129 | 855 | 0.280 |40 minutes|Less than |Hay and|June |Male. | | | | 8 hours| oats | | 130 | 800 | .300 |30 minutes|Less than | do. | do. | Do. | | | | 18 hours| | | 131 | 860 | .280 |20 minutes| do. | do. | do. | Do. 135 | 955 | .150 |1 hour 50 |6 days | do. | do. | Do. | | | minutes | | | | 134 | 740 | .160 |3 hours |4 days | do. | do. | Do. (1)137| 925 | .150 |50 minutes|6 days | do. | do. | Do. (1)136| 1,000 | .150 | do. |Survived | do. | do. | Do. 126| 980 | .200 |20 minutes|27 hours | do. | do. | Do. 127| 760 | .200 |1 hour |28 hours | do. | do. | Do. 128| 1,075 | .200 |3 hours |7 hours | do. | do. | Do. ------+--------+-------+----------+----------+--------+------+--------

(1) Subcutaneous injection for comparison.

SUMMARY.

A survey of the results obtained in experiments on guinea pigs shows that the mode of introduction of caffein exerts but little influence on its toxicity. On careful analysis it will be observed that the rate of absorption after the administration of caffein by mouth, subcutaneously, or intraperitoneally is about the same for the time of appearance of symptoms. The persistence of the symptoms of caffein intoxication observed in these experiments for 24 hours after administration points to slow elimination, which may be expected, owing to the fact that the guinea pigs passed but little urine and caffein is not diuretic for these animals. The prolonged presence of caffein in the body probably exerts a harmful influence or after effect, which may account for the delayed death of some animals many days after a single dose of caffein was given. Among the factors which undoubtedly influence toxicity, season should be considered, while the presence of a diseased condition undoubtedly tends to decrease the resistance of the guinea pig to caffein. Diet was without any influence on the toxicity of the single dose of caffein.

EXPERIMENTS ON CATS.

These experiments were performed on well-fed animals which were kept under observation for several days before the tests with caffein were made. The diet consisted of meat exclusively. In some cases the urine was examined for albumin and sugar before caffein was given. No tests with caffein were made if large amounts of albumin were found. It may be remarked that sugar was never found in cats before the administration of caffein, but that considerable amounts of it were found in some cases after it was given. Studies by various modes of administration were made, by subcutaneous injection, intraperitoneally, or by mouth. Attention was also directed to the resistance to caffein in young cats, several experiments on kittens being made with this object in view.

SUBCUTANEOUS INJECTION.

Rost stated that caffein is eliminated in the urine unchanged after its introduction into the body and that the amounts found varied with different species of animals. In the rabbit the amount eliminated was about 21 per cent; in the dog about 8 per cent; and in the cat somewhat less than 2.5 per cent. It would appear, therefore, that the cat decomposes caffein more readily than the rabbit or dog; its resistance consequently ought to be greater than that of the other animals. Moderately large doses were accordingly employed in the preliminary experiments (series A), but the results obtained, as shown in the protocols, indicated that caffein is fully as toxic for the cat as for the rabbit or dog. The doses were then decreased and experiments were performed in order to ascertain the smallest toxic as well as the smallest fatal dose.

SERIES A.

Three decigrams of caffein per kilo were administered in these experiments. The results are shown in the following protocols:

Cat 4. Black and white. Weight, 1,440 grams.

May 26: 10.05 a. m., 22 cc 2 per cent caffein (0.3 gram per kilo) injected subcutaneously; 11.10 a. m., copious salivation, cat irritable, muscular stiffness present, but no tetanus; 11.45 a. m., cat restless, convulsions, attacks of short duration, no paralysis observed after the convulsions, pupils dilated; 4.45 p. m., cat quiet, slight paralysis present.

May 27: Cat exhausted.

May 28: Found dead.

Cat 5. Black and white male. Weight, 1,396 grams.

June 3: 10 a. m. 21 cc of 2 per cent caffein (0.3 gram per kilo) injected subcutaneously; 12 noon, found dead.

Although there was considerable difference in the duration of life following the injection of the same dose of caffein per kilo, the final outcome was the same, as both cats died from the effects of the drug. One died within 2 hours and the other lived more than 30 hours after its administration. Three decigrams of caffein per kilo is, therefore, surely fatal to these animals. Tests made with smaller doses are shown in the following experiments: