The Effect of Methylxanthines on the Hypocoagulability Induced by Chloroform in the Dog

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Abstract
1. The oral administration of a single or two consecutive daily doses of chloroform to dogs, induced hypoprothrombinemia and lowered the fibrinogen level. Both changes from the normal were most marked 48 hours after chloroform administration. By resting the dogs about 2 weeks between trials comparable reductions in the plasma prothrombin and fibrinogen levels were realized. 2. When caffeine, theobromine, theophylline and adenine were given orally to dogs prior to the oral administration of chloroform and continuing for five consecutive days, the hypoprothrombinemia was either markedly reduced or completely prevented. Creatine, creatinine, guanidine or uracil also afforded some protection. Guanine, xanthine, arginine, allantoin, uric acid or urea gave practically no protection. 3. Caffeine, theobromine, theophylline and adenine also prevented a reduction in the plasma fibrinogen level during chloroform intoxication. Uracil and guanidine showed some protective action, while creatine, creatinine, guanine, xanthine, uric acid, allantoin, urea and arginine gave no detectable protection. 4. Liver injury from the chloroform, as reflected by the bromsulfalein test and icteric plasma, was readily detectable when the methylxanthines or adenine were given with the chloroform, even though no change in prothrombin or fibrinogen level was apparent. 5. It appears that a definite relationship exists between the purine bases (caffeine, theobromine, theophylline and adenine) and the specific function of the liver to elaborate plasma prothrombin and fibrinogen. The capacity of the liver to synthesize prothrombin apparently can be affected independently of other normal functions.