82 THE TOXICITY OF CAFFEIN. 



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 subcu- 

 taneously, 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 peri- 

 cardial 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 haying 

 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. 



December 6: Weight, 9.90 kilos; 11.35 a. m., received 25 cc 2 per cent caffein solu- 

 tion by subcutaneous injection in back; 4 p. m., no symptoms, appetite good. 



December 7-9: Received 25 cc caffein 2 per cent solution subcutaneous injection, 

 no symptoms, area of injection inflamed and swollen. 



December 10, 13: Site of injection showed increased inflammation, received 0.495 

 gram caffein (50 mg per kilo) in 30 grams meat daily without showing any symptoms. 



December 14: 12 noon, received 0.7425 gram caffein by mouth (0.075 per kilo); 2.30 

 p. m., restless and uneasy. 



December 15: 11.30 a. m., received 0.7425 gram caffein by mouth; 2 p. m., depressed 

 in spirits, although continues to have good appetite. 



December 16: Weight, 9.50 kilos; 3.15 p. m., received 0.9509 grain caffein by 

 mouth; 4.50 p. m., no symptoms. 



December 17: Animal rested. 



December 18: Received 0.950 gram caffein by mouth, no symptoms. 



December 19: Received 0.9509 gram caffein by mouth, no symptoms. 



December 20: 2.45p. m., received 1.1875 grams caffein (0.125 gram per kilo); 4 p. m., 

 restless and quite sick; ate only a little food. 



December 21: 9 a. m., still uncomfortable, allowed to rest, no caffein given, grad- 

 ually recovered appetite. 



December 22: 11 a. m., received 1.875 grams caffein; 3 p. m., seemed sick, but 

 showed no other symptoms, appetite fair. 



December 23: 9 a. m., showed no symptoms from the day before, ate food grad- 

 ually, seemed sick; 11.30 a. m., received 1.425 grams caffein (0.150 gram per kilo); 1.30 



