22 
two important modifications since it was originally published, but 
otherwise it is essentially the same. He employs frogs (Rana tem- 
poraria) which are collected not earlier than the end of June. They 
are kept in a cellar in a box the bottom of which is covered with 
water, the latter being changed at least daily. The frogs should 
not be used before the third day of captivity and should be brought 
to the examining room six hours before they are needed, being placed 
in jars at a temperature not over 17° C. The examinations should be 
carried out in July, August, and September, during which months 
the susceptibility of the frogs does not differ greatly, and also during 
this time no distinction need be made with reference to sex. Animals 
weighing between 25 and 30 grams are selected and fastened to a 
board in the usual manner, and the heart is exposed without allowing 
bleeding or other injury (pithing is not permitted at this time). 
After opening the pericardium a slight pressure upon the abdomen 
will cause the heart to protrude from the opening, where it will remain 
in plain view. A measured quantity of the infusion to be tested is 
now injected into the two leg lymph sacs, about 0.3 c. c. into each or 
0.6 c. c. in all. Both lymph sacs are used so that the distended skin 
will not force the drug out of the opening by pressing upon a large 
bulk of fluid. Systolic standstill of the heart is now watched for and 
it should appear in ten or fifteen minutes. When this is observed 
and the time noted, the frog is pithed and weighed. 
Two more frogs are now selected of about the same weight, and the 
dose to be injected is determined by the effect of the primary dose. 
If the heart, in the first frog, stopped in less than ten minutes, a 
relatively smaller dose is used, while if it did not stop in twenty 
minutes a larger dose should be employed. A sufficient number of 
frogs should be used so that four are found in which the hearts have 
stopped between seven and twenty minutes. The toxic value (V) 
of the drug is then determined in relation to the size of the frog (P) 
divided b} r the dose of the drug given (d) multiplied by the time it takes 
p 
for the heart to come to a svstolic standstill (t ) : ( V) = BBU The “Vs,” 
J dxt 
having been determined for each trial, are averaged and the amount 
found is considered as representing the value of the preparation of 
digitalis which has been tested. Focke considers that a good speci- 
men of leaves should give a standard value of 5. He originally 
accepted all readings between ten and twenty-five minutes, but the 
method was modified later to time limits of seven to twenty minutes, as 
he found the results were much more uniform. If the heart stops in a 
shorter time than seven minutes, the differences in the values found 
are greater, or if over twenty minutes, he found the readings were 
much more variable, and the “Vs” obtained were very small. For 
this reason he dislikes Ziegenbein’s and Frankel’s methods, the former 
