Part 20

SERIES D.

A 0.5 per cent caffein solution was used in these experiments in order to test the effect of concentration on its toxicity; the rate of injection was 1 cc per minute.

Rabbit 569. Gray male. Weight, 1,475 grams. Diet, oats.

February 6: 11.50 a. m. to 12.01 p. m., injected 10 cc 0.5 per cent caffein; 12.03 to 12.12 p. m., injected 10 cc of 0.5 per cent caffein; 12.13 to 12.26 p. m., injected 10 cc of 0.5 per cent caffein, total amount injected, 30 cc; 12.20, passed 35 cc of urine; 12.30, increased reflexes, but no convulsions; 4 p. m., reflexes increased.

February 11: Alive, condition good.

Rabbit 574. Gray female. Weight, 1,555 grams. Diet, oats.

February 8: 10.25 to 10.33 a. m., injected 4 cc of 0.5 per cent caffein in salt solution, injection discontinued for five minutes; 10.38 to 11.10, injected 30 cc, total amount of caffein solution received, 34 cc; 11.55 a. m., very sensitive; reflexes markedly increased.

February 9: Alive, condition good.

Rabbit 571. Gray female. Weight, 1,530 grams. Diet, oats.

February 7: Injection 3.18 to 3.50 p. m., received 30 cc in 32 minutes, not hypersensitive; 3.55, restlessness and weakness of extremities; 4.10 p. m., control of anterior extremities impaired, distinctly paretic but tried to walk about, died the same afternoon.

Rabbit 568. Gray male. Weight, 1,605 grams. Diet, oats.

February 7: Injection 10.53 to 11.01 a. m., injected 10 cc 0.5 per cent caffein; 11.03, injection resumed after two minutes interval; 11.14, received 10 cc 0.5 per cent caffein intravenously in 11 minutes; 11.16, injection resumed; 11.35, received 12 cc 0.5 per cent caffein, total amount of caffein solution received, 32 cc; 12.30 p. m., urinated 14 cc of bloody urine; 12.55 p. m., convulsions and death a few minutes later. Autopsy showed congestion of viscera, but no other lesions.

Rabbit 570. Gray female. Weight, 1,225 grams. Diet, oats.

February 7: 2.06 to 2.35 p. m., injected 24.5 cc 0.5 per cent caffein, reflexes increased but no convulsions, paresis especially marked in the anterior extremities; 3 p. m., passed urine which was normal in appearance, reflexes not increased but rabbit was weak.

February 9: Found dead. Autopsy: Liver, spleen, and kidneys congested; large intestines hemorrhagic; omentum congested and showed the presence of small caseous nodules; liver showed adhesion to diaphragm; viscera presented the appearance of intraabdominal infection.

Of the five rabbits of this series three died as a result of the administration of caffein. The other two which survived showed mild symptoms only, such as increased reflexes, but no evidence of severe poisoning such as was observed after the injection of the same doses of caffein in series A when a 2 per cent solution of caffein was injected. Convulsions were noticed in one case only (No. 568); paresis in two cases (Nos. 570 and 571). The nervous symptoms even in this group, therefore, were much milder than in series A. The percentage of death, however, was greater than in series A, in which the concentration of caffein was four times as great. It is quite probable that the strain on the heart due to the sudden increase in volume of the blood and its dilution might be an important factor in increasing the toxicity of caffein. It is conceivable that doses just sufficiently large to depress the normal heart may cause paralysis of an already overstrained organ.

SERIES E.

In the two experiments of this series the rate of injection as a possible factor influencing the toxicity of caffein was tested. A 2 per cent caffein solution was injected at the rate of 1 cc in two and one-half to three minutes.

Rabbit 572. Gray male. Weight, 1,770 grams. Diet, oats.

February 8: Injection began at 3 p. m., discontinued at 3.37 p. m., and resumed at 3.38 p. m.; rabbit was restless; injection finished at 3.52 p. m. Total quantity received, 17.4 cc 2 per cent caffein intravenously in 52 minutes; struggled intermittently during the injection; anterior legs paralyzed.

February 9: Found dead.

Rabbit 573. Gray male. Weight, 1,810 grams. Diet, oats.

February 8: Started to inject at 1.35 and discontinued at 2.27 p. m.; received 18 cc 2 per cent caffein intravenously in 52 minutes; reflexes markedly increased soon after; 2.45, passed bloody urine; 4.30 p. m. reflexes increased; no other symptoms.

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

It will be observed that some retardation of the onset of symptoms was caused by slower injection, but the final result was the same as when the injections were made more rapidly. It is quite probable, therefore, that a much slower rate of injection may lessen considerably the toxicity of caffein.

From the results of the experiments by intravenous injection summarized in the table, it appears that the minimum toxic dose for rabbits of a 2 per cent caffein solution, injected at the rate of 1 cc per minute, is about 50 mg per kilo. Twice the dose induces severe symptoms and may be fatal; 160 mg per kilo are surely fatal. If the rate of injection is diminished, the toxicity of caffein is lessened, but this effect is not marked unless the injections are very slow. Dilution of the caffein solution suppresses to some extent the nervous symptoms, but the toxicity, on the contrary, seems to be increased.

TABLE 5.--Intravenous injections.

SERIES A.