THE MAST CELLS 



the blood by the suprahepatic veins and soon causes spasm of their sphincters. 

 The liver swells and its lymph drainage is enormously increased, flushing the 

 heparin into the general circulation by way of the thoracic duct. Once the 

 normal route for histamine is closed by spasm of the suprahepatic sphincters 

 the remainder of the histamine will accompany the heparin in the lymph. 



I suggested this hypothesis of peptone shock at the Histamine Symposium 

 (p. 407). Later, Dr. West and I sought the experimental data to test its validity. 

 We cannulated the thoracic duct in the thorax of three dogs (after resecting 

 some of the lower left ribs to gain access to the posterior surface of the pleura) 

 and took repeated samples of blood and lymph both before and after injecting 

 peptone into the portal, or into a femoral, vein. Unfortunately, we had no 

 facilities for keeping dogs beyond the stage of the acute experiment, and we 

 felt that the results obtained with such preparations were open to objection 

 from several points of view. It is also difficult to find and cannulate the thoracic 

 duct without first giving the dog a fatty meal; but if this is done, the induction 

 of peptone shock becomes more difficult since dogs do not give a well-marked 

 response to peptone unless they have been starved for some hours beforehand. 

 Nevertheless, we found that the first histamine does enter the blood directly 

 very early in the shock and that the heparin lags behind and reaches the blood 

 almost exclusively through the thoracic duct. Normal lymph clots, as does 

 blood plasma. In peptone shock the thoracic duct lymph soon becomes 

 incoagulable. It is of interest that White and Woodard (1957) have since shown 

 that our unpublished data were sound. 



Fate of heparin in the rat treated with a histamine-liberator 



Further evidence against the view that heparin from the tissue mast cells 

 is a natural anticoagulant was obtained by comparing conditions in the dog 

 and rat. There are very few mast cells in the liver of the rat, though they are 

 common in the peritoneum and are extremely numerous in the connective 

 tissue. One might therefore expect this connective tissue to be the 'shock 

 organ' of the rat and to release both histamine and heparin into the blood if 

 the older views on heparin are correct. 



The following experiment was carried out to test this point (Riley et al, 

 1955). Two groups of eight female Wistar rats, of 200-250 g., were used. The 

 first received intraperitoneally over a period of five days progressively increasing 

 doses of compound 4880 in saline, by which time 1 mg. per 100 g. body- 

 weight could be given without eliciting signs of shock. The second group was 

 given equivalent volumes of saline intraperitoneally as a control. Whole 

 blood clotting times were measured repeatedly by the capillary tube method, 

 and samples of urine, collected on filter paper, were tested for metachromatism 

 with a weak solution of toluidine blue. At the end of five days the two groups 



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