538 ANAPHYLAXIS 



forerunner of death. Symptoms appear about ten minutes after the 

 injection has been given; occasionally in pigs not very susceptible they 

 are delayed thirty to forty-five minutes. Animals developing late 

 symptoms are not very susceptible and do not die. Death usually 

 occurs within an hour, and frequently in less than thirty minutes. If 

 the second injection be made directly into the brain or circulation, the 

 symptoms are manifested with explosive violence, the animal frequently 

 dying within two or three minutes" (Rosenau). 



H. Pfeiffer has shown that a depression of the temperature is a con- 

 stant finding in the severer forms of anaphylaxis in the guinea-pig. In 

 fatal cases this decrease may be as much as from 7 to 13 C. Some 

 relation exists between the extent and the duration of the fall of temper- 

 ature and the severity of the symptoms. During acute anaphylaxis the 

 blood shows a leukopenia, a diminution in complement, and, as shown 

 by Friedberger, 1 a delay in or a loss of coagulability. The most striking 

 change observed after death is permanent distention of the lungs, resem- 

 bling emphysema, described by Gay and Southard, and particularly by 

 Auer and Lewis. 2 The lungs do not collapse, but remain fully distended, 

 forming a cast of the pleural cavities. The alveoli are distended, and 

 in some instances the walls may be ruptured. The walls of the second- 

 ary and tertiary bronchi are contracted, with infoldings of the normally 

 thick mucosa, due to contraction of the smooth muscle by peripheral 

 action, death really resulting from inspiratory immobilization of the 

 lungs. The heart continues to beat long after respiration has ceased. 

 Rosenau 3 and Gay and Southard 4 have also described minute hemor- 

 rhages in various organs and mucous membranes. 



The amount of serum necessary to sensitize a guinea-pig is sur- 

 prisingly small. Rosenau and Anderson found one guinea-pig that was 

 sensitized .by 0.000,001 c.c. As a rule they used less than 0.004 c.c. in 

 their experiments. Besredka places the minimum amount necessary 

 to secure uniform results at 0.001 c.c., whereas 0.0001 c.c. proved suf- 

 ficient in a considerable percentage of animals. The sensitizing dose of 

 horse serum ordinarily employed in experiments upon guinea-pigs is 

 0.01 c.c. ; amounts ranging from 0.001 c.c. to 1 c.c. are ordinarily followed 

 by an incubation period of from ten to sixteen days. Large doses also 

 sensitize, but a longer incubation period is required. In order to pro- 

 duce a fatal result, the second or intoxicating dose must be considerably 



1 Zeitschr. f. Immunitatsf., 1 orig., 1909-1910, 8, 636. 



2 Jour. Exp. Med., 1910, xii, 172. 3 Bull. No. 32 of the Hyg. Lab., 1906. 

 4 Jour. Med. Research, 1908, xix, 1, 5, 17. 



