136 The Chemistry of the Injured Cell 



observation that prior depletion of bodily stores of histamine, 

 adrenaline and 5-H.T. by repeated injections of the histamine 

 liberator compound 48/80 renders animals resistant to the onset of 

 shock otherwise induced by a variety of means (Zweifach, 1958) . 



FERRITIN (VDM) AND THE LIVER 



It is possible to demonstrate in the blood in the early stages of 

 shock, a substance that sensitises vessels to the action of adrenaline. 

 This substance has been called vaso-excitor material (VEM) but 

 has not been fully characterised nor has its possible role in shock 

 been elucidated. It is believed, however, to originate in the ischae- 

 mic kidney. 



Another substance with the opposite property of depressing 

 vascular reactivity to adrenaline is present in the blood in the later 

 and deeper stages of shock. This is known as vasodepressor material 

 (VDM) and has been characterised as a derivative of an iron-bind- 

 ing protein, ferritin (Shore et al., 1951) . The source of VDM is 

 the liver and its formation may be an indication of the abnormal 

 circulatory condition of the liver in shock. It may be significant that 

 viviperfusion of the liver with arterial blood protects against the 

 onset of shock in traumatised animals (Zweifach, 1958) . On the 

 other hand, the presence of VDM in the circulation need not in- 

 dicate a general effect on the blood vessels of the body since its 

 appearance in the blood may indicate merely an "overflow" from 

 the liver. VDM may be formed from ferritin by reduction to the 

 — SH form, due to accumulation of reduced xanthine oxidase due 

 in turn to increased purine metabolism in the liver (Green et al., 

 1956) . The iron may undergo chelation to form a complex akin to 

 cytochrome c, capable of catalysing the oxidation of adrenaline. 



BACTERIAL PRODUCTS 



In the past decade there has been a revival of interest in the 

 possibility that bacterial products, in particular those absorbed 

 from the intestine, might contribute to the phenomena of shock 

 (Fine et. al., 1952) . A great deal of evidence has now been collected 

 bearing on this point. Bacterial endotoxin (obtained chiefly from 



