ANAPHYLAXIS OR HYPERSUSCEPTIBILITY 299 



At reinjection, the symptoms are most severe when the injection is 

 made intravenously. 



The symptoms which follow on the reinjection of antigen into sensitive 

 animals may show a wide range of variation according to the degree of sensi- 

 tiveness and amounts injected. In acute anaphylaxis of guinea-pigs, which as 

 you know has been the most thoroughly studied, there is a rapid and severe 

 death which may not occupy more than a fraction of a minute or at most five 

 to ten minutes. The animals repeatedly show restlessness, cough, pass urine 

 and feces, develop severe dyspnea, with infrequent respiration in which there 

 seems to be almost complete immobilization of the chest wall and in which 

 finally only shallow, irregular, spasmodic efforts take place. This, as Auer and 

 Lewis have shown, is due to tetanic contraction of the small bronchioles, with 

 occlusion of the air passages, practically no air entering the lungs. As the 

 dyspnea develops, there may be at the same time spasmodic twitching of the 

 limbs, retraction of the head and general convulsions. 



When for some reason or other the reaction is not so severe the animal 

 may show merely general signs of illness, ruffling of the fur, twitching and 

 restlessness, with respiratory difficulty of varying degree, coughing, and evacua- 

 tion of urine and feces. In rabbits the symptoms are often less rapid in de- 

 velopment, but in general principles are similar; in rabbits there is more fre- 

 quently in the moderate cases a gradual muscular weakness in which the an- 

 imal lies flat on the ground unable to support itself on its legs, a condition 

 which may proceed for long periods. Death is largely respiratory and the 

 heart may continue to beat for a long time after respiration has completely 

 stopped. There is a sinking of blood pressure and a depression of temperature. 



The coagulation time of the blood is lengthened, there is apparently a depres- 

 sion of the leukocytes, and according to a number of investigators, who have 

 been recently confirmed by Behring, there is a disappearance of blood platelets 

 and an increased flow of lymph. 



Pathologically in an animal dead of anaphylaxis there may be petechial 

 hemorrhages, according to Gay and Southard, in the heart muscle, pleura and 

 intestinal wall and there may be fatty degeneration of the vascular endothelium. 

 In guinea-pigs especially there is a marked emphysematous dilatation of the 

 lungs which is very constant, although according to Doerr it is not absolutely 

 characteristic of this condition. Apart from the anatomical changes following 

 acute anaphylaxis, frequently repeated injections of small doses of horse serum 

 or egg white in dogs, cats, rabbits and guinea-pigs have been shown by Long- 

 cope to produce cell injury in various organs, especially in the liver, myo- 

 cardium and kidneys. 



When sensitized animals recover from the second injections, they 

 are thereafter immune that is, they do not react to subsequent in- 

 jections of the same substance. 



