C. H. BEST 



sheep, pork, beef, and dog tissues are 1:2:5:10. While proteins dif- 

 fer with the species, there are few known examples of species variations 

 occurring with polysaccharides. Chemical studies of heparin would 

 therefore be of interest from several points of view. 



The body contains enormous amounts of heparin. A dog 

 weighing ten kilograms contains approximately ten thousand units of 

 heparin, or sufficient to prevent clotting of ten kilograms of blood. 

 This is all contained in the tissues, since none can be detected in 

 normal blood. What is the function of such a large store of heparin? 

 It has been suggested that it provides an emergency mechanism which 

 can prevent intravascular thrombosis by the liberation of heparin into 

 the vessel threatened by thrombosis. Histological studies have demon- 

 strated that heparin is localized in the mast cells located in the walls 

 of blood vessels. Such a position would be suitable for a function of 

 this nature. Heparin is liberated from the mast cells and found in the 

 blood in peptone and anaphylactic shock. What is the initial stimulus 

 to heparin liberation? Is it the appearance of thrombin, of fibrin, or 

 the agglutination of platelets? How much heparin is liberated in 

 twenty-four hours? Is this increased when there is tissue damage, 

 as after operations? Does the heparin content of the mast cells and 

 tissues remain constant, or does it change with age, sex, operations, 

 etc.? Many of these questions could be quickly answered if we had 

 accurate methods for the determination of heparin in blood and tissues. 

 However, the amount in blood is too small for estimation by our present 

 methods, and the only procedure applicable to other tissues is to 

 attempt isolation by the method developed for one particular tissue — 

 beef lung. 



On injection, heparin rapidly disappears from the blood. An 

 enzyme, heparinase, has been prepared from rabbit liver. The puri- 

 fication and study of the distribution of this enzyme has not yet been 

 attempted. 



Heparin prevents the clotting of blood and the agglutination 

 of platelets, but we still do not know the mechanism of the action. 

 Heparin when added to oxalated plasma and thrombin prevents the 

 clotting of this system. However, if fibrinogen is substituted for the 

 plasma, heparin has no effect. This action of heparin on clotting 

 therefore depends on the presence of some unknown plasma factor. 

 The anticoagulant efTect of heparin on blood does not depend on this 



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