40 THE TOXICITY OF CAFFEIN. 



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. 



j 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 hyper- 

 sensitive; 3.55, restlessness and weakness of extremities; 4.10 p. m., control of ante- 

 rior 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 dilu- 

 tion might be an important factor in increasing the toxicity of caffein. It is conceiv- 

 able 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 influ- 

 encing 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 



