peutic intervention is possible if the investigator is in the dark concerning these points. The first attempt to study anaphylaxis more thoroughly was made by Arthus in 1903. This investigator showed for the first time that anaphylaxis in rabbits is characterized by a marked drop in blood pressure. This drop in blood pressure Arthus considers the most delicate indicator of anaphylaxis. In 1910 Cesaris-Demel described the effects which were produced when the excised heart of a sensitized rabbit was perfused with a dilute solution of the same proteid which caused sensitization. He stated that such a heart rapidly decreased the amplitude of its beat and assumed a condition of greater tonus; toxic effects were also noted on normal hearts, but by no means as pronounced as in sensitized hearts. In 1911 Auer showed independently that the heart of an intact anaphylactic rabbit of sufficiently high sensitization rapidly fails to do its work, and that the animal succumbs for this reason. The functional basis for this heart failure was shown to be a complete or almost complete loss of direct irritability of the heart ventricles. On macroscopical examination of the heart muscle, the right ventricle shows a toughening of the muscle bands on its endocardial surface when scraped by the finger nail. The left ventricle does not show this toughening, except now and then on its papillary muscles. The same observer also demonstrated that these cardiac changes were obtained after section of the vagi, and after destruction of the central nervous system, thus proving that the fatal cardiac reaction was not due to central, nervous influences, but was of peripheral origin. He also noted the absence of any marked disturbance of the lungs in anaphylactic rabbits.
In dogs, Biedl and Kraus, and later Arthus, proved that the main symptom of anaphylaxis was a rapid, profound and long-lasting drop in blood pressure. Experimental evidence led Biedl and Kraus to the view that this fall was due to a paralysis of the vasomotor endings in the splanchnic area. Associated with this drop in blood pressure the same observers noted a diminution in the number of leucocytes, and an extreme loss of coagulability of the blood. Blood drawn from a dog during the anaphylactic state remained fluid for many hours, sometimes days. The respiratory function showed no noteworthy alterations. The dogs recovered as a rule.
The functional alterations produced by anaphylaxis in guinea-pigs is entirely different from those observed in rabbits and dogs. In the guinea-pig, Auer and Lewis showed that the functional interference occurs in the lungs. Within a few seconds after the intravenous injection of an adequate "second" dose the animal shows greater and greater difficulty in getting air into and out of its lungs, until finally a stage is reached where no air at all enters on inspiration and this in spite of the fact that the animal makes most violent inspiratory attempts. Three
