380 



Drs. J. W. Pickering and J. A. Hewitt. 



appearance from the liver of the excess of alkali secreted under the toxic 

 stimulus. 



The next experiment, No. 21, shows that if relatively large amounts of 

 'peptone" are injected slowly, in minimal doses, over a long period of time, 

 into a cat in which the circulation through the liver has been prevented, then, 

 as in the intact animal, no anticoagulant action is to be obtained. 



Experiment No. 21. — Cat, Z\ kilos. Pithed, artificial respiration. Aorta 

 ligatured beyond the coronary arteries, inferior vena cava above the 

 diaphragm. 



Over period of 1 hour 10 minutes l - 8 grm. of " peptone " in - 9 per cent. 

 NaCl was injected in nine equal amounts, each injection being 2'5 c.c. in 

 volume and being made at approximately equal intervals of time. 



The coagulation times of the blood was taken at frequent intervals during 

 the injection of the " peptone " and at no time showed any delay. 



Control Blood on Glass. — Commencement of clotting, 9 minutes ; comple- 

 tion of clotting, 12 minutes 10 seconds. 



The total amount administered was 1*8 grm., and as only about one-fourth 

 of the animal's blood was circulating, the concentration of "peptone" in the 

 blood at the end of the experiment may be estimated at 3 - 6 per cent., an amount 

 much in excess of that required to produce anticoagulant action both in 

 whole cats and in cats in which the liver is not acting, provided that such an 

 amount is injected slowly. Moreover, reference to Experiment No. 10 shows 

 that a concentration of 3'5 per cent, of peptone in the blood in vitro produced 

 incoagulability over a period of 24 hours. Assuming in the in vivo experi- 

 ment mentioned above that the quantity of blood dealt with was 50 c.c, a 

 concentration of " peptone " exceeding that required to produce prolonged 

 incoagulability in vitro was injected without anticoagulant effect. 



Some other explanation must therefore be sought for this immunity to the 

 slow injection of " peptone " than is supplied by the divergent views of Nolf and 

 of Mellanby. These hypotheses have one point in common, they assign the 

 cause of immunity to hepatic secretion, and it is precisely this point of both 

 theories which is shown to be untenable by the experiments given above. 

 Whether the alkali reserve or the hydrion concentration of the plasma is 

 concerned in these occurrences must be left for future determination. There 

 are, however, some indications which point in this direction. Eano (loc. cit.) 

 showed that peptone blood could be clotted either by the passage through 

 it of carbon dioxide or by neutralisation by acid. Earlier in the present 

 paper the influence of the concentration of carbon dioxide in circulating 

 blood on the action of "peptone" has been emphasised. It is noteworthy 

 that Mills (48) has recorded that a diminution of the alkali reserve occurs 



