26 
According to their results it appeared that 1 gram of the tincture 
would kill a 59-gram frog, trnt the water soluble active constituents 
would only kill a 15-gram frog. The 44 grams difference in frog 
weight therefore ought to be killed by the insoluble portion or digi- 
toxin. The toxic value for the digitoxin for only a 17-gram frog had 
been demonstrated by the Keller method, however, leaving 27 grams 
of the toxicity of the digitoxin of the original tincture still unac- 
counted for and which probably remains in the resinous portion when 
Keller’s method of determination is used. In other words, only 
about one-third to one-half of the digitoxin present is isolated by this 
method, and the authors conclude, therefore, that the only reliable 
method for the assay of digitalis tinctures is the physiological one. 
Freund a studied the action of abyssinin and compared it with 
drugs of the digitalis groups, notably, digitalin, digitalein, digalen, 
the dialysate of digitalis, and strophanthin. 
For the purposes of this investigation he used frogs and rabbits. 
With the former the heart was laid bare and attached to a suspension 
writing lever, thus obtaining tracings showing the progressive action 
of the drug. In some animals a solution of the drug was dropped 
directly on the heart, while in others it was injected into a lymph sac. 
In the case of rabbits Freund used the blood pressure changes as a 
method for comparing the relative action of the drugs. 
In his study of the different heart drugs, Kakowski & examined a 
number of digitalis preparations, among them being the infusion and 
the tincture. He employed the isolated hearts of frogs (R. tempo- 
raria), rabbits, cats, and dogs and showed that the infusion acted more 
strongly upon some of the animals than the tincture. 
Still another modification of the use of a frog’s heart in estimating 
the activity of members of the digitalis group was adopted by San- 
tesson c in his examination of the strength of different varieties of 
strophanthus seeds. In this method the drug was injected into a 
lymph sac of It ana temporaria. The animal was not tied down, but 
was held on its back in such a way that the contractions of the heart 
could be observed through the skin. Incase it was necessary, a glass 
rod was passed into the esophagus so as to press the heart forward 
to facilitate the determination of its rate. Finally, to allow of exact 
timing of the appearance of the systolic standstill, the chest was 
opened and the organ observed directly. The standard dose employed 
by Santesson was that amount of the drug which would produce 
systolic standstill of the heart in thirty minutes, the dose being 
reckoned upon the basis of a 50-gram frog. Santesson’s custom was 
to give a large dose at first, one that would be sure to kill, and on 
a Freund, Zeitschr. Exp. Path. u. Therap., 1905, I, 557. 
b Kakowski, Arch. Internat. de Pharmacod. Gand et Par., 1905, XV, 21. 
c Santesson, Skandi. Arch. f. Phys., 1905, XVII, 389. 
