Part 45

December 15: Received 0.4725 gram caffein by mouth, no symptoms.

December 16: Received 0.655 gram caffein, 0.100 gram per kilo.

December 17: No caffein given.

December 18: Received 0.655 gram caffein daily, 0.100 gram per kilo, no symptoms.

December 20: Received 0.8188 gram caffein, 0.125 gram per kilo, no symptoms, appetite good.

December 21: Received 0.9825 gram caffein, 0.150 gram per kilo, somewhat uncomfortable, no other symptoms.

December 22: Received 0.9825 gram caffein, 0.150 gram per kilo, no symptoms except some uneasiness.

December 23: 9 a. m., no symptoms, appetite good; 11.30 a. m., received 1.146 grams caffein, 0.1759 gram per kilo; 1.30 p. m., died while making an effort to get out of cage, tonic contraction of limbs observed before death.

The amount of caffein received during the entire experimental period was 9.2223 grams, or an average per day approximately of 80 mg per kilo, and therefore 10 per cent more than dog No. 30 received. It will be observed that the appetite in dog No. 32 was likewise uniformly good, and that he received a very high protein diet which was also of a very high calorific value.

Autopsy (dog 32).--Stomach presented a severe inflammation of the mucosa, especially in the fundus and pyloric portions. The gastritis was more marked in pyloric portion, and the inflammatory condition extended along the whole course of small intestines, which presented numerous hemorrhagic areas, and a thick catarrhal exudate on the mucosa. The large intestine contained quite a large number of parasites, probably round worms. The liver was enlarged and the gall cyst well filled. The spleen was also considerably engorged, kidneys appeared normal, other organs all appeared normal.

Dog 31. Black spaniel, male.

This dog had been under observation one month previous to the experiments with caffein. The usual initial dose was then administered for nine days. There were no signs of local irritation when the drug was given subcutaneously, but symptoms of toxicity were present. These disappeared, however, when the drug was administered by mouth. The dose was therefore increased to 75 mg per kilo. This, as will be seen, proved fatal within six hours. High nitrogen diet, same as No. 30.

November 3: Weight 10.250 kilos.

November 10: Weight, 10.25 kilos.

November 20: Weight, 10.30 kilos.

December 1: Put in cage.

December 6, 7, 8, 9: Weight, 10.20 kilos; received 26 cc 2 per cent caffein subcutaneously, site of injection normal.

December 6: Very restless and excited, whined when handled as though muscles were sore, appeared to be sick.

December 10-14: Condition good, received 0.51 gram caffein by mouth daily, no noteworthy symptoms, appetite continues good, somewhat restless at intervals.

December 15: 11.30 a. m., received 0.765 gram caffein per mouth (0.075 gram per kilo); 2 p. m., depressed in spirit, seemed sick and uncomfortable; 4.15 p. m., when about to feed, animal jumped up, then fell back dead.

Autopsy (dog 31): Lungs congested; heart filled with blood and contained small amount of blood-stained fluid in pericardial sac. Liver deeply congested, soft and friable; gall bladder distended with bile; kidneys showed inflammation of cortex; spleen pale, normal in size and consistency; stomach practically empty, the mucosa of the pyloric portion exhibited severe gastritis, with thick catarrhal exudate. This catarrhal inflammation extended through the duodenum; remaining portion of small intestine showed mild inflammation; large intestine appeared practically normal. The total amount of caffein received by dog 31 during 10 days was 5.395 mg, or a daily average of 53.9 mg per kilo. This unusually low resistance to caffein (which was practically the only case in all the experiments on dogs presented in this research) suggests the presence of some abnormal condition. The bloody exudate in the pericardial cavity indicating pericarditis, which is likely to induce secondary changes of cardiac muscle, may be considered as a possible cause of the increased toxicity of caffein in this case.

Dog 29. Male fox terrier, black.

This dog was kept on a low nitrogen diet for nearly five weeks before the feeding of caffein was begun. The administration of 50 mg of caffein per kilo was then carried on for eight days without showing any symptoms of toxicity. The usual increase of dose was then given--75 mg per kilo--which was followed by a manifestation of symptoms. Further increase, however, to 100 mg per kilo had no visible effect. Nevertheless it was considered advisable to suspend the feeding of caffein for one day. The same amounts were then repeated on two consecutive days. No symptoms having been observed, 125 mg per kilo were given. As symptoms of toxicity and especially loss of appetite were observed, the dog was not given any caffein the next day. Since his appetite had now improved, the experiment with larger doses was resumed. Death followed after the second dose of 150 mg per kilo. Protocol follows:

Weight, 9.90 kilos. One-third nitrogen diet. Receives 0.269 gram nitrogen per kilo (88.269 calories per kilo).

November 3: Weight, 9.85 kilos.

November 10: Weight, 9.55 kilos.

November 12: Weight, 9.40 kilos.

November 29: Weight, 9.85 kilos.