13 
DETERMINATION OF HEART ACTION. 
The popular belief in the value of caffeine in preventing the poi- 
sonous heart effects of the coal-tar products suggested the experi- 
mental determination of any modifications in the action upon this 
organ which might occur when it was exliibited in combination with 
acetanilide. Experiments were carried out upon both warm and cold 
blooded animals, using the myocardiograph method to record the 
changes in the dog’s heart, the perfusion method in estimating the 
changes in the frog’s heart. 
Action upon the frog’s heart . — The perfusion method was adopted 
as being most suitable for determining the changes occurring in the 
frog’s heart after acetanilide and combinations of this drug with 
caffeine citrate or an alkaline carbonate. This method was believed 
to be especially suitable for this purpose on account of the relative 
insolubihty of acetanilide in an aqueous solvent, since compara- 
tively small amounts are sufficient to produce profound changes in 
the isolated heart. It is also of advantage because by its use second- 
ary and extraneous effects are excluded, any action being limited 
to the intrinsic nerves of the heart or to the cardiac muscle substance. 
In all cases frogs of the same variety (Rana pipiens) captured at 
the same time and kept under the same conditions were used. As 
far as possible those of the same weight were chosen and this was 
always done when comparisons between the relative effects produced 
on several frogs were to be noted. In most instances each heart was 
made its o^vn control, so that these precautions were usually unnec- 
essary. The frogs were pithed (both brain and cord) and the heart 
exposed in the usual manner. After removal of the pericardial sac 
the right branch of the aortic arch was dissected out and ligated, and 
a canmda inserted into the left branch as far from the heart as pos- 
sible. By gentle traction upward the heart may be separated from 
the oesophagus and other tissues, best accomplished by running a 
bhmt dissecting needle between these structures and the sinus venosus. 
If the animal is small it is probably easier to insert the inflow camiula 
into the posterior vena cava by turning the heart over vdth the base 
downward (frogs weighing 10 grams have been successfully employed 
using this procedure). If the animal is large, 25 to 50 grams, the 
venous cannula is usually inserted with the heart lying in the normal 
position. 
Two Mariotte bottles of about 150 c. c. capacity were used to hold 
the perfusing fluid. They were mounted on a stand and into the 
upper opening of each bottle a glass tube reaching to within one-half 
c. m. of the bottom was inserted through a tightffi fitting stopper in 
order to allow ingress of air and thus preserve a constant pressure no 
matter what the level of the fluids m the bottles might be. The 
outlets of the two bottles were connected through a Y tube held 
