Part 30

Cat 24. Striped. Weight, 1,300 grams.

October 25: 10 a. m., 50 cc urine, albumin moderate amount--no sugar; 10 cc caffein injected subcutaneously at 12 noon; 12.30, irritable, cried persistently, no appetite; 4 p. m., no convulsions, but persistent crying.

October 27: Cat was still alive.

Cat 17. Weight, 2,620 grams.

October 12: 9.30 a. m., 65 cc urine collected; more than a trace of albumin present, no reduction of Fehling's solution; 3 p. m., 20 cc 2 per cent caffein (150 mg per kilo) injected subcutaneously; 3.15 p. m., irritable and restless.

October 13: 9 a. m., about 15 cc urine collected, reduction of Fehling's solution marked; osazone test also positive.

Cat 23. Black and white. Weight, 1,645 grams.

October 25: 10 a. m., 140 cc urine collected (since October 23), small amount of albumin present, no sugar.

October 27: 9 a. m., no albumin; no sugar in urine; 11.50 a. m., 12.5 cc caffein injected subcutaneously (0.15 gram per kilo); 1 p. m., convulsions and death.

Cat 7. Striped kitten. Weight, 1,285 grams.

October 11: Urine collected, no albumin, no sugar; 9.50 a. m., 10 cc 2 per cent caffein injected subcutaneously in the back; 10.10, violent convulsions lasting about 30 seconds; 10.20, convulsions of shorter duration; 10.30 convulsions; 10.35, convulsions lasting a few seconds; urine passed about 10.20, contained a moderate amount of albumin, but there was no reduction of Fehling's solution; 10.45, profuse salivation and paralysis; died about 10.50.

Cat 39. Yellow. Weight, 2,285 grams.

April 13: 2.40 p. m., 16 cc 2 per cent caffein (0.14 gram per kilo) injected subcutaneously in the back; 3.45 p. m., cat died.

Of the five experiments of this series three died after doses of 140, 150, and 155 mg per kilo. The other two showed symptoms of toxicity, but survived a dose of 150 mg per kilo which indicated that the minimum fatal dose was probably reached. To test this supposition smaller doses were administered, as shown in the following experiments.

SERIES D.

Ten cats were used for this series of experiments, and the doses administered varied between 103 and 139 mg per kilo. The results shown in the appended table (p.58) indicate that about 120 to 140 mg of caffein per kilo may induce mild symptoms in some cases. The conclusion may be safely drawn therefore that 150 mg per kilo is approximately the minimum fatal dose for the cat when the drug is given subcutaneously. That smaller doses are, however, by no means to be regarded as always safe is shown in the following experiments.

SERIES E.

Cat 43. Weight, 3,225 grams.

Cat probably old; had been in the laboratory for several weeks before the experiment. Gained in weight 175 grams.

September 14: 10.20 a. m., 20 cc 2 per cent caffein (0.124 gram per kilo) injected into the back; 11 a. m., tetanus and death. Autopsy: Lungs congested; liver congested and showed hemorrhagic spots in capsules and fatty degeneration; kidneys slightly congested; other organs normal.

Cat 48. Black female. Weight, 3,050 grams.

September 14: 18 cc 2 per cent caffein (0.118 gram per kilo) injected subcutaneously in the back; 10.30 a. m., violent convulsions and death. Autopsy: Lungs congested in spots showing numerous petechia; liver congested; spleen congested; other organs normal.

The diminished resistance to caffein of cats Nos. 43 and 48 might be due to the pathologic changes found on autopsy, for evidence is not wanting that the toxicity of drugs might be greatly altered under pathological conditions. Hunt(40) has shown that resistance to acetonitril is considerably diminished in chronic alcoholism. This seems to be true also of other drugs under abnormal conditions. Smaller doses of atropin(78) are required in lead poisoning than under normal conditions to produce the same results. The following experiment is of interest in this connection, for in this case a much smaller dose than was given in experiments Nos. 43 and 48 produced the typical symptoms of caffein poisoning and proved to be fatal.

Cat 47, black and white male. Weight, 4,220 grams.

September 15: Received subcutaneously 18 cc 2 per cent caffein (0.084 gram per kilo); no symptoms observed for about six hours.

September 16: No symptoms.

September 17: Weight, 4,250 grams; injected 18 cc 2 per cent caffein (0.084 gram per kilo); tetanus and death after two hours. Autopsy: Severe hemorrhagic pneumonia; kidneys pale, other organs normal.

Since two controls survived the same dose in proportion to the body weight of the animal without showing any symptoms, the assumption is justified that the lower resistance to caffein was due to the presence of pneumonia, thus affording additional support to the view that the toxicity of caffein may be increased in disease.