SHOCK 307 



and from capillaries respectively. Normally the values are equal; in 

 shock on the other hand the venous blood is much concentrated, which 

 indicates that plasma must have left the blood in the capillaries. 



To understand the nature of the process by which this loss of blood occurs 

 in the capillaries, it is important to digress here to consider the results 

 obtained by H. H. Dale and A. N. Richards 53 on the effects of histamine on 

 the circulation. It is by an application of the work of these investigators 

 that much light has been thrown on the shock problem in recent years. 



Evidence Obtained by a Study of the Shock Produced by Histamine. 

 Histamine is derived by removal of the carboxyl group, as C0 2 , from 

 histidine, one of the most important of the building stones of the pro- 

 tein molecule. Injected quickly into etherized animals in very minute 

 dosage (1 mg. per kg. body weight) histamine soon causes the arte- 

 rial blood pressure to fall to the shock level of 30-40 mm. Hg. For a brief 

 period preceding the fall there is a rise in pressure due to constriction of the 

 arterioles, and this constriction persists while the pressure is falling. So far 

 as the obvious vascular changes are concerned, therefore, the condition -is 

 strictly comparable with those found in shock low blood pressure and con- 

 stricted arterioles. By the time the pressure has fallen to near the shock 

 level the cardiac pulsations disappear from the tracing. The respirations 

 also cease, but if the animal be kept alive by artificial respiration and the 

 thorax opened for inspection of the heart this organ will be observed to be 

 beating quite vigorously, with, however, a pronounced deficiency of blood 

 in the auricles and in the large veins both of the thorax and abdomen. 

 This observation affords positive proof that in this form of shock at least 

 the fundamental cause for the condition is inadequate blood flow to the 

 heart. The question is, what becomes of the blood? Either it must pass 

 out of the blood vessels into the tissues, or the capacity of the former must 

 be increased. Loss of blood itself could scarcely occur short of hemorrhage 

 of which there is no evidence in histamine shock but the water with some 

 of the soluble constituents (plasma) might become extravasated, leaving in 

 the vessels blood excessively rich in corpuscles. Such extravasation ac- 

 tually occurs in acute histamine shock, as revealed by measurement either 

 of the concentration of hemoglobin or of the corpuscles, but this in itself 

 cannot explain all of the loss in circulating blood, for if the histamine be 

 given slowly (over a period of 20-30 min.) it takes much longer for the 

 shock to become established, and the blood does not show any increase in 

 the percentage of hemoglobin or in the number of corpuscles. In these 

 cases we are driven to conclude that much of the blood must be withdrawn 

 from currency by stagnation in dilated vessels. Direct evidence for this 

 important conclusion has been secured by determination of the volume of 



