48 Professor W. M. Bayliss [Feb. 13, 



left the body. But why do the former cases also appear to be suffer- 

 iiir from the same condition, when scarcely any blood has actually 

 been lost ? 



In the endeavour to find an explanation for this, we may call to 

 mind the circumstance that blood may be effectively removed from 

 circulation by being pooled away in some part or other of the vascular 

 system, as, for example, by a great dilatation of this part. The 

 amount which is available for propulsion by the heart to serve for 

 continuous irrigation of the tissues is reduced as much as it would be 

 if the blood held in the pool were actually lost to the outside. Such 

 changes in the capacity of the peripheral blood-vessels play a large 

 part in the regulation of the blood-pressure and the supply of blood 

 to various organs. We may inquire whether anything of this kind 

 happens after severe injuries. 



The first step taken in the course of this enquiry was the discovery 

 that some poisonous substance is produced in injured tissues. This, 

 passing into the blood, is carried to all parts of the body. Sir 

 Cuthbert Wallace, some years ago, had noticed that operations in 

 which the cutting of large masses of tissue was involved were 

 especially liable to be followed by shock. Quenu and others, during 

 the war, were struck by the rapid benefit frequently ensuing from 

 removal of the injured parts or even when they are tied off from 

 connection with the rest of the blood-vessels, if such is possible. 

 Cannon and myself found that we could produce the state of wound- 

 shock in anaesthetised animals in the laboratory, and that it was due 

 to a chemical agent, not to any effect on nerves. This being so, 

 we see that we can replace the name of " wound-shock " by the more 

 descriptive one of " traumatic toxaemia." 



But can we form any conclusion as to the chemical nature of this 

 toxic substance or as to the way in which it acts ? It is evidently 

 produced too quickly to be a result of bacterial infection, and, indeed, 

 McNee was able to exclude this possibility quite definitely. Dale 

 and Laidlaw, however, showed that there is a compound of known 

 chemical structure, called " histamine," and produced without difficulty 

 from a constituent of the nitrogenous cell structures, which is able 

 to produce a state of the circulation like that present in wound-shock, 

 ir was found that the effect was not due to a dilatation of the arterial 

 part of the system, as was known to be the case in the fall of blood- 

 pressure brought about by vaso-motor reflexes. Here the similarity 

 to traumatic toxaemia showed itself again, because it was known that 

 arterial dilatation was not present in this state. Next, Dale and 

 Richards, by a number of ingenious experiments, were able to localise 

 the effect in the capillaries, which became widely dilated and thus 

 capable of taking up the greater part of the blood in the body, leaving 

 the heart nearly empty, with too meagre a supply to carry on the 

 circulation with any degree of efficacy. It is to be" admitted that we 

 have not yet definite proof that it is histamine itself which is 



