ELECTROCARDIOGRAM, MYOCARDIAL ACTION POTENTIAL 
AND CARDIAC EXCITABILITY IN LABORATORY ANIMALS 
E. Lepeschkin' 
As the result of personal studies and findings from 
the literature, a comparison is made between the most 
important electrocardiographic and cardiac electro- 
physiologic characteristics in a number of experimental 
laboratory animals in order to determine which animals 
are most similar to humans and can therefore be used 
to study problems arising in human pathology. Refer- 
ence is made to the trans-membrane action potential, 
conduction disturbances, the T and U waves, cardiac 
pacing and defibrillation as well as tissue culture. In 
the choice of the appropriate experimental animal and 
method of study, convenience, cost, freedom from arti- 
facts and the possibility of unphysiological experimental 
conditions must be taken into consideration as well as 
similarity of function and structure to those of the 
human heart. 
INTRODUCTION** 
While studies applicable in all respects to 
human electrocardiology can be best conducted 
in humans, it is obvious that certain experi- 
mental studies, especially those carrying the 
risk of cardiac damage, can be carried out only 
in experimental animals. Certain basic prop- 
erties of cardiac muscle can be studied with a 
minimum of cost and equipment in cold-blooded 
animals, while others require experiments in 
primates, where the structure of the heart and 
its position in the thorax closely approximate 
those of humans. In the following we shall con- 
sider which of the commonly used experimental 
animals are best suited for the study of the 
most important clinical problems in electrocar- 
diography and cardiac electrophysiology. Be- 
cause of time limitations we shall confine our- 
selves to problems involving the ventricles. 
• Department of Medicine, University of Vermont, College of Medi- 
cine, Burlington, Vermont. 
Supported by the U. S. Public Health Service Research Grant 
HE-01486 and by the Research Career Award HE-K6-440 from the 
National Heart Institute to Dr. Lepeschkin. 
LABORATORY ANIMALS 
The Frog 
The frog as an experimental animal offers 
the advantage of low initial cost and upkeep, 
and because of its low oxygen consumption 
and respiration through the skin, access to 
the heart is possible without the inconvenience 
of artificial respiration. Since the frog ventricle 
has a sponge-like structure and no blood vessels, 
strips of ventricular muscle are much less likely 
to suffer hypoxia than hearts of animals which 
ordinarily depend on a blood supply through 
blood vessels. Furthermore, because the heart 
is normally at room temperature, its surface 
can be exposed without the distortion of the T 
wave and S-T segment which is unavoidable 
when the heart of warm-blooded animals is ex- 
posed to the air. 
As can be seen from Table I, the resting and 
action potentials of the frog ventricle are quite 
comparable to those of human hearts, and the 
basic ionic mechanisms of excitation and re- 
polarization are similar.^'^ ® Although the mus- 
cle fibers are smaller than those of mammals, 
they can be more easily penetrated in situ be- 
cause of the less vigorous heart beat. However, 
the plateau is longer and the T wave more 
pointed than in man, and because the ventric- 
ular action potential is sensitive to acetyl cho- 
line, the T wave is much more variable than in 
mammals.* There are no Purkinje fibers and the 
muscle fibers have no transverse tubules, and 
the conduction velocity is much slower than in 
mammals. Because of this the frog heart can 
be easily used for the study of ventricular fi- 
brillation (this can be done only in the larger 
mammals). 
Another property of frog myocardium in 
which it deviates appreciably from man and 
other mammals is the excitability curve. Since 
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