14 
CARDIAC MODELS 
mg%. At autopsy the animals that had been fed 
the "average diet" had about 75% of their aor- 
tic intimal surface involved with pale smooth 
plaques and fatty streaks, v^^hile the animals fed 
the "prudent diet" had only about 10 to 15% of 
the surface involved. No reference could be 
found in their report to the status of the coro- 
nary arteries of these animals. This study pre- 
sents evidence that the serum lipid levels of rhe- 
sus monkeys can be increased and aortic 
athei-osclerosis exacerbated when the animals 
are fed diets physiologic for human beings. 
Manning, Clarkson, and Lofland have re- 
ported on cholesterol absorption, turnover, and 
excretion rates of hypercholesterolemic rhesus 
monkeys.'" Cholesterol-l,23H was incorpo- 
ated into the diets for 195 days and during the 
isotopic steady state 83 to 92% of the serum 
cholesterol was derived from dietary choles- 
terol; thus, 8 to 17% was derived from syn- 
thesis. The monkeys consumed about 550 mg of 
cholesterol per day (from a semi-synthetic diet 
containing 25% lard and 1 mg/calorie choles- 
terol) and absorbed from 127 to 192 mg per 
day. The percentage of fecal total steroids in 
the form of bile acids varied, ranging from 26 
to 47% of the total endogenous cholesterol ex- 
creted daily. 
Rhesus monkeys have been used to study cho- 
lesterol metabolism following surgical ileal 
bypass.-^ Following ileal bypass there was a 
decrease in plasma cholesterol concentration 
that was followed by a return to preoperative 
concentrations. Experiments were done to 
measure the rates of hepatic cholesterol biosyn- 
thesis and it appeared that the secondary rise in 
plasma cholesterol concentration was due to in- 
creased synthesis of cholesterol in the liver. 
It is now apparent that the addition of fat 
and cholesterol to the diet of rhesus monkeys in- 
duces a marked hypercholesterolemia and a se- 
vere form of atherosclerosis both in the aorta 
and coronary arteries. The wide use of rhesus 
monkeys in atherosclerosis research was no 
doubt because initial attempts to produce hy- 
percholesterolemia and/or atherosclerosis were 
not successful. Sperry et al. found that the con- 
centration of serum cholesterol did not change 
significantly during eight hours after the inges- 
tion of several eggs and that there was only a 
slight increase after the eggs were fed for sev- 
eral days.-® When crystalline cholesterol was 
given orally as an emulsion for four days no 
rise in the cholesterol concentration of serum 
occurred. Heuper fed two laboratory-born juve- 
nile rhesus monkeys cholesterol — containing 
diets.-" After eight months the animals were 
examined at necropsy and no atherosclerotic le- 
sions were found. Heuper concluded that rhesus 
monkeys "do not readily react to a prolonged 
nutritional intake of excessive amounts of cho- 
lesterol with a formation of atheromatous aor- 
tic lesion." There is no good explanation for the 
observation of Heuper. 
Taylor and his co-workers pioneered the 
early studies on diet induced atherosclerosis of 
rhesus monkeys. They reported that the 
addition of fat and cholesterol to the diet re- 
sulted in extensive aortic and coronary artery 
atherosclerosis as well as cutaneous and tendon- 
ous xanthomatosis. Since then their work has 
been confirmed by numerous investigators.^*-^^ 
The anatomic distribution and the pathogene- 
sis of rhesus monkey atherosclerosis bears a 
striking resemblance to that in man. Lesions de- 
velop first in the aorta, iliac arteries, and caro- 
tid sinus. Coronary artery atherosclerosis 
follows in its development with the proximal seg- 
ments of the epicardial coronary arteries devel- 
oping lesions almost as rapidly as the aorta. 
When hypercholesterolemia is present for more 
than 18 months the lesions tend to become 
larger and more complex and new lesions ap- 
pear in the peripheral arteries such as the distal 
coronary intramyocardial branches, mesenteric, 
spleenic and femoral arteries and the basal cir- 
culation of the brain. Complications of lesions 
such as vascularization, calcification and throm- 
bosis are prominent after 36 months of hyper- 
cholesterolemia. 
Armstrong and his co-workers^" have com- 
pared the cholesterol content of numerous tis- 
sues of normocholesterolemic and hypercholes- 
terolemic rhesus monkeys. The most notable 
increases in tissue cholesterol concentration 
were seen in liver, spleen, skin, tendon, muscle 
and adipose tissue in addition to the increases 
that might be cardiovascular tissues. 
The striking increases in skin and tendon 
cholesterol content is the result of the remark- 
