Experimental production of gross atherosclerosis in the rat.
Gross atherosclerosis was produced in the rat by feeding purified diets containing cholesterol, sodium cholate, and thiouracil for periods up to 363 days. In a few weeks a marked increase of the serum cholesterol and beta lipoproteins as well as of the liver lipides was observed. Lesions visible in the gross were found on the intimal surfaces of the vessels of all 46 animals examined. These were most prominent in the heart valves and aortic arch. The earliest lesions, which were seen at 31 days, required Sudan staining for gross demonstration. Older lesions were visible without staining. Microscopic coronary artery lesions were present and in one instance were accompanied by massive myocardial infarction. Vascular lesions were characterized by medial and intimal lipide infiltration and cellular intimal plaque formation. In a part of this study the protein level of the diet was altered at the expense of sucrose. The hypercholesteremic response among the rats varied according to the dietary protein level. The lowest response was observed among those animals receiving the highest level of dietary protein. A difference, however, in the severity and extent of the arterial lesions among these relatively small groups of rats could not be established under these experimental conditions. In all these experiments a close correlation existed between the serum cholesterol levels and beta lipoproteins of the S(f)20-100 range.