Alfred G. Karlson

THE USE OF GUINEA PIGS IN STUDYING CHEMOTHERAPY OF EXPERIMENTAL TUBERCULOSIS

For the protection of the patient concerned, animal experimentation must precede clinical trials of a substance having alleged antituberculosis properties. In view of the chronic protracted nature of the disease in man and the long periods of treatment, it must be she-n by experiments on animals that a drug will produce no serious or irreversible morbid changes when administered for long periods. In addition, it must be demonstrated that the proposed chemotherapeutic agent is capable of effecting regression and healing of an active tuberculous process which has been established in animals by inoculation of virulent human tubercle bacilli. Tests designed to determine the bacteriostatic or bactericidal properties of a substance against the tubercle bacillus in rlilro and tests of prophylaxis i r z zho, in which treatment is started before or at the same time as infection, will yield desirable information. An analysis of the therapeutic potential of a chemotherapeutic agent, however, can be made only by studying, in animals, its ability to cause arrest and repair of a progressing destructive disease which has been demonstrated to exist before therapy wns started. Adequate information on the potentialities of a chemotherapeutic agent in experimental tuberculosis may be gained only by therapeutic tests on more than one species of animals susceptible to infection. However, one must select the animal most suited to the particular objective of an experiment] whether it be a problem of screening large numbers of compounds, tests of therapeutic efficiency, or experiments to determine the effect of immunity on chemotherapy . The universal use of guinea pigs for many years in routine diagnosis and investigational work in tuberculosis provided a background of experience and information on tuberculosis in these animals which was not generally available for other species. The guinea pig was selected, therefore, as the animal especially suitable for chemotherapeutic testing in which the objective of the tests is to detect any beneficial change due to therapy in the morbid processes of a progressing disease. Such a test in guinea pigs requires that the animals be infected with a virulent strain of tubercle bacillus capable of producing a predictable amount of disease and that the disease be advancing and well established before treatment is started. The evidences of control and healing, such as fibrosis and calcification, are determined by histologic examination.

Experimental Bacterial Endocarditis Due to Streptococcus Mitis

It is important in order to advance the increasingly successful attack on subacute bacterial endocarditis to be able to produce the disease experimentally and to treat it with new and improved therapeutic regimens. Since endocarditis caused by Streptococcus mitis has not been consistently produced previously in the dog, a study was undertaken in which cardiovascular stress was created by the establishment of aortico-inferior vena caval and bilateral iliofemoral arteriovenous shunts. After a period of antibacterial treatment and of stabilization, daily intravenous injections of broth cultures of S. mitis were begun. In 50 per cent of 24 animals bacterial endocarditis developed, simulating that found in clinical cases at necropsy. These animals had widely patent fistulas and 11 showed evidences of congestive heart failure. Of the remaining 12 animals, five with patent fistulas died of the effects of multiple infected pulmonary emboli. Seven others whose shunts had closed were killed and found to have no significant lesions other than healed caval infections.