PHYSIOLOGY AND BIOCHEMISTRY OF SHOCK 409 



State within the white blood elements; the small remainder circulates 

 in a free state in the plasma or is held within the red blood corpuscles. 

 In the so-called "shock" tissues as the lungs of the guinea pig and the 

 liver of the dog, predominant amounts of histamine are present. Here, 

 likewise, histamine, in the normal animal, is held in an inactive state, 

 but is assumed to constitute a rich and ready source for toxic action. 



Halpern (1945) reported that a very high level of histamine and 

 histamine-like substances has been found during attacks of asthma and 

 in the blood, urine and sputum of allergic patients. Related to this, 

 asthmatic victims are found to be extremely sensitive to histamine. In 

 urticaria and Quincke's edema, the histamine has often been found to 

 be very high in the blood. In certain sick headaches and during painful 

 crises of gastroduodenal ulcer a high level of histamine has been found. 

 Nevertheless, Halpern concludes his discussion in the following 

 manner. "However, we think that the study of histamine cannot itself 

 furnish us with decisive clues. We think that the action of histamine 

 confines itself to strictly local reactions a'p'pearing at the very level of the 

 tissues or the organ which constitutes what is called the 'shock organ.' 

 Generally speaking, histamine is destined to be formed to die on the 

 spot. It is only exceptionally that histamine spreads throughout the 

 circulatory system. The measurement of circulating histamine, there- 

 fore, is only a relative value and as long as we do not know the local 

 munifestations, that is to say the tissue modifications of histam^ine, we 

 can formulate more or less vague hypotheses only." 



In connection with the above stated destruction of histamine at the 

 site of its liberation the observations of Granroth and Nilzen (1948) 

 are of interest. They demonstrated that extracts prepared from the 

 skins of guinea pigs, rabbits, cats and human subjects exercise high 

 histaminolytic activity. [For the destruction of histamine in various 

 mammalian tissues see Zeller (1942), and for a discussion of data in 

 support or opposed to the histamine theory of allergy and anaphylaxis, 

 see Ratner (1943)]. 



c. Origin of Histamine. Tissue histamine might be considered as a 

 decarboxylation product of the naturally occurring 1-histidine. Werle 

 and Krautzun (1938) reported the formation of histamine from the 

 decarboxylation of 1-histidine by the kidney and liver tissues of guinea 

 pig, rabbit, hamster and mouse; a trace of decarboxylase was observed 

 in the pancreas of guinea pig, rabbit and hamster. It is interesting to 



