MODEL OF ADVANCED CORONARY ATHEROSCLEROSIS, 
MYOCARDIAL INFARCTION AND SUDDEN DEATH 
WITH LETHAL ARRHYTHMIAS IN SWINE 
K. T, Lee, J. Jarnnolych, D. N. Kim and W. M. Lee* 
The purpose of this study was to develop a model in 
swine for advanced coronary atherosclerosis and my- 
ocardial infarction. The approach was to combine a 
number of techniques that were thought to induce the 
development of atherosclerosis, including high-fat, high 
cholesterol diet plus propylthiouracil and x-irradiation 
to the precordial region. The dose of x-irradiation that 
was used produced minimal changes by itself, but 
seemed mainly to enhance the effect of atherogenic diets. 
In series I among 28 swine fed the severe atherogenic 
diet and x-irradiated twice, 24 developed myocardial in- 
farcts. All had advanced coronary atherosclerosis. 
Twenty-two died "suddenly" in the sense that no clini- 
cal signs of illness were observed prior to death. In se- 
ries II among 33 swine fed the moderate atherogenic 
diet and x-irradiated twice, 29 died suddenly. All had 
advanced coronary atherosclerosis, and 25 had my- 
ocardial infarcts. Terminal ECGs taken on 7 swine 
showed either ventricular fibrillation or ventricular 
asystole. Among 32 swine fed the severe diet and x-ir- 
radiated twice, 28 died suddenly. All had severe coro- 
nary atherosclerosis, and 26 had myocardial infarcts. 
Terminal ECGs taken in 9 swine showed either ventric- 
ular fibrillation or ventricular asystole. 
INTRODUCTION** 
A moderate degree of coronary atheroscle- 
rosis can be produced in swine by feeding a sim- 
ple semi-synthetic diet containing a large 
amount of cholesterol.^ More severe lesions can 
be produced if bile salts and propylthiouracil 
are added to the diet containing cholesterol. 
Even with these additives, a year or more is re- 
quired to produce advanced atherosclerotic le- 
sions with significant luminal narrowing.- In 
swine examined in previous experiments these 
slowly developing coronary arterial lesions have 
not been associated with myocardial infarction, 
sudden death or other manifestations of coro- 
nary heart disease. 
The purpose of the current study was to de- 
velop a model in swine for advanced coronary 
* Department of Pathology, Albany Medical College and VA Hos- 
pital, Albany, New York 
*• Supported by NIH Contract 69-2050 and HE 14177 
atherosclerosis with its complications similar to 
those seen in man. Such a large animal model is 
presently needed for the scientific trial of thera- 
peutic devices and surgical procedures prior to 
their use in man. Since the object was to de- 
velop a model for study of effects of advanced 
atherosclerosis, it was not considered essential 
that the etiology and pathogenesis of the lesion 
be precisely the same as in man. It was only 
necessary that the induced disease have clinical 
and anatomic features reasonably similar to 
those in man. For the model to be of maximum 
usefulness, it should be possible to produce ad- 
vanced lesions in a reasonably short time. The 
approach chosen in the current study was to 
combine a number of techniques thought to en- 
hance the development of atheroclerosis, includ- 
ing high-fat, high-cholesterol, bile salts, propyl- 
thiouracil and x-irradiation. It is well known 
that the effect of cholesterol feeding on arteries 
can be intensified by x-irradiation. In earlier 
studies with other species we have shown that 
intensification can be accomplished with doses 
of x-ray that produce little effect on arteries 
when given without cholesterol feeding. Using 
this approach, we have been able to rapidly pro- 
duce occlusive coronary artery disease with my- 
ocardial infarction and sudden death in swine 
by the combined techniques of atherogenic diet 
and x-irradiation. 
MATERIAL AND METHODS 
The current study has been carried out in two 
series. Series I has been completed^ and Series 
II is in progress. Male miniature swine of Pit- 
man-Moore strain were used. The number of 
swine used for Series I was 100 and for Series 
II was 80. All were weanlings weighing 8-10 kg 
at the outset of the experiments. Table I shows 
the composition of three types of atherogenic 
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