INTRODUCTION 17 



in cats. In 1913 Hoskins and McPeek showed that light massage of the 

 suprarenal glands leads to a similar fall of blood pressure. 



Again, if the suprarenals normally pour into the blood stream enough 

 secretion to maintain a significant augmentation of pressure, sudden occlu- 

 sion of the suprarenal veins should result in a prompt depressor effect. 

 This follows from the fact that epinephrin is quickly removed during the 

 passage of the blood through the capillary bed. As a matter of fact, 

 such occlusion characteristically leaves the pressure precisely where it 

 was before. The depression which ultimately appears occurs only after a 

 matter of hours or in some cases even of days. 



Hoskins and McClure tested the theory in another way. If dilute 

 epinephrin be injected into a vein at a very slow but gradually increasing 

 rate, at first no effect at all is seen. Then various changes occur. The 

 earliest of these is depression of intestinal peristalsis. If simultaneous 

 records of peristalsis and blood pressure are taken it is found that the 

 gut is paralyzed before any rise of blood pressure occurs. One need 

 scarcely point out the unliklihood that blood pressure is normally main- 

 tained by any mechanism that involves gastro-intestinal paralysis. . Among 

 physiologists the tonus theory has on such grounds largely been discarded ; 

 but among clinicians it is still occasionally invoked to account for various 

 symptoms. 



But the fact remains that suprarenal extirpation leads to death and 

 the final symptoms include a failure of functions that are under sympa- 

 thetic control. Elliott (1905) has offered the interesting suggestion that a 

 minute quantity of circulating epinephrin is necessary, not to stimulate 

 the sympathetic system, but to maintain its irritability ; that in its absence 

 the terminal neurocellular substance of the sympathetic system is no 

 longer able to transmit impulses. This possibility also was investigated 

 in the writer's laboratory. It seemed that animals at the point of death, 

 such as Elliott studied, should not be deemed capable of giving any very 

 significant information. All sorts of secondary factors might have entered 

 into the experiment. If sympathetic failure is a characteristic feature of 

 the syndrome, it should appear at an early stage. Experimentally it 

 was found that at a time when the animal deprived of its suprarenals, 

 was showing marked symptoms, when it could scarcely sustain its own 

 weight, its vasomotor system responded to stimulation perfectly well. The 

 observation was repeated upon numerous animals. Hence sympathetic 

 failure following suprarenal extirpation is to be regarded as a secondary 

 feature. Both cardiac and muscular weakness precede it. It would seem 

 probable that if, as Elliott supposed, a trace of epinephrin is essential 

 for sympathetic function, the vasomotor reaction should be improved if 

 an animal previously deprived of its suprarenals were to receive a con- 

 tinuous injection of very dilute epinephrin for such a period, for instance, 

 as half an hour. By direct experiment the surprising fact was discovered 



