EXPERIMENTAL STUDIES ON HEART TONICS IV. THE MAIN FACTORS OF DIGITALIS STANDARDIZATION WITH A NEW ASSAY METHOD

¹ From the Research Laboratories of the New Jersey College of Pharmacy, Rutgers University

A study of the important factors of digitalis standardization led to the following conclusions:

1. Warm-blooded animals are to be preferred as test material to animals lower in the animal scale and to plants.

2. The best way of administering heart tonics in the assay is the intravenous injection.

3. The new intravenous anaesthesia is to be preferred to the former methods of narcosis in animal experimentation in general, for the standardization of heart tonics in particular.

4. The drop of the blood pressure to zero, as shown by the kymographic tracing, approaches closest the theoretically expected endpoint of the experiment and thus is to be preferred to the observation of the stoppage of the heart and the general death of the animal.

5. The time of the experiments should be kept as uniform as possible. This precaution is necessary in view of our newer knowledge of the distribution of digitalis in the body and with reference to the differences as to beginning and duration of the pharmacological action of the various active constituents of the heart tonics.

6. One of the main handicaps of all the methods of digitalis standardization in use at present is the fact that both tinctures and infusions need preparation prior to the test. These procedures, as evaporation of alcohol and water and great dilution of the alcoholic solution precipitate active constituents thus decreasing the strength of the preparation to be tested at random. A practical assay method should avoid any such injurious manipulation.

Based on the study of these principal factors a practical method of digitalis standardization is described using the rabbit as test animal. This method has the following advantages: The animal material is always easily available. The end point of the assay obtained by means of the drop of the blood pressure, supplementing the test by the use of ouabain, is definite and as close to the theoretical endpoint as may be expected. Because of the higher resistance to digitalis the method allows the testing of drugs of high concentration as well as drugs of great dilution without preliminary injurious manipulations of the heart tonics.