THE ACTION OF THE LETHAL DOSE OF STROPHANTHIN IN NORMAL ANIMALS AND IN ANIMALS INFECTED WITH PNEUMONIA.
The results of these experiments permit a comparison of the action of strophanthin in the normal and the infected animals. In cats the percentage of deaths following the injection of 0.1 mg. of strophanthin per kilo of body weight was the same in normal and in pneumonic cats. The number of recoveries in this series was larger than was expected. This result was due to the fact that the dose injected was not the lethal dose, but the average lethal dose (0.1 mg.) determined by Hatcher and Brody (7) and by Eggleston (8). The doses which the latter actually injected ranged from 0.085 rng. to 0.16 mg.; from these the average minimal lethal dose was calculated. In adopting the average dose as the standard one to inject, those of our cats that required more than 0.1 mg. naturally survived. The death rate was therefore low. The plan employed in dogs differed from that used in cats. A lethal dose was injected in each dog. Death occurred when an average of 0.12 mg. of strophanthin per kilo of body weight was injected. The same dose was required in normal and pneumonic dogs. The effect of strophanthin in both groups of infected and non-infected cats and dogs is, therefore, identical. Whether the uniformity of strophanthin action in the two experimental groups may serve as the basis for assuming a like uniformity of action in normal individuals and in pneumonia patients is a subject which requires further analysis. The difficulty in transferring the experimental results to patients lies in the question of whether the type of pneumonia produced in animals is the same as that found in man. Clinically, the two diseases present both resemblances and differences. The animals become definitely ill and show the symptoms already described. The illness, however, is of short duration and apparently reaches its height in the majority of animals in twenty-four to seventy-two hours. Before the expiration of this time, the temperature frequently returns to normal. Many of the infected animals, when they survive, recover in three to five days. The mortality in dogs infected with pneumococci is given by Lamar and Meltzer as 16 per cent. In the present series of twelve infected cats, the mortality was also 16 per cent. These findings differ from human pneumonia in the following particulars: The infection is not so severe; the temperature, though elevated at first, soon falls; the duration of the disease is short; and convalescence is rapid. The mortality is slightly lower. Musser and Norris (12) give the human mortality at 21.06 per cent. Pathologically the two diseases also show differences. The gross appearance of the lungs is not dissimilar, but in the animals the consolidated portions are somewhat dry and they fail to show a stage of gray hepatization (5). The amount of fibrin present is small. There is comparatively slight congestion of the alveolar walls and of the walls of the bronchi. The relation of experimental pneumonias to the human disease has been discussed by a number of investigators. Almost all believe that the two types are similar, if not identical. Among the first to express this opinion was Sternberg (13) ; and later Gamaleia (14), Prudden and Northrup (15), Kinyoun and Rosenau (16), Wadsworth (17), Lamar and Meltzer (5), Wollstein and Meltzer (9) coincided with his view. Lamar and Meltzer, especially, have insisted on the identity of the two processes. On the other hand, Welch (18) in his study of experimental pneumonia, says: "Many inoculations of cultures of virulent pneumococci into the trachea and lungs of dogs have been made in my laboratory by Dr. Canfield and myself, but in no instance were we able to produce an inflammation of the lungs which we were willing to identify with acute lobar pneumonia as found in human beings." But he adds that, in the majority of experiments, there was no demonstrable consolidation and that pleurisy and more or less extensive areas of pneumonia were produced only in a few animals. The inference consequently cannot be drawn that an effect obtained with strophanthin in the experimental disease may be anticipated in man. The striking similarity in action in infected and uninfected animals renders it likely, however, that the usual action of the drug in man may be expected in the presence of pneumonia. We have accumulated evidence, to be published later, which shows that this action actually takes place in the human disease. As far as evidence obtained electrocardiographically is concerned, our experiments show that strophanthin causes the same electrical changes in the heart when the animals are infected as it does under normal conditions.
Hospital of The Rockefeller Institute for Medical Research.
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Jamieson