Spontaneous Coronary Arteriosclerosis in Repeatedly Bred Male and Female Rats

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Abstract
Repeatedly bred male and female rats of several strains develop arteriosclerosis spontaneously, irrespective of diet. The severity of the lesions differs between male and female breeders. The morphology and pathogenesis of these lesions have been found to be the same in all of the strains examined. Once the process of arteriosclerosis has been initiated within the abdominal aorta, the subendocardial and medium-sized myocardial coronary arteries also show degenerative changes. The large epicardial coronary arteries become arteriosclerotic only when the process of arteriosclerosis has become severe and generally distributed throughout the aorta. The smaller subendocardial lesions are characterized by occlusive swelling of medial muscle cells and by the presence of vacuoles. These vacuoles react negatively to lipid stains but stain positively for mucopolysaccharide. The myocardial arteries show endothelial hyperplasia, elastosis and accumulations of mucopolysaccharides, especially in the region of fragmented elastic elements. The mucopolysaccharide-rich endothelial cushions eventually become fibrosed. The epicardial arteries show intense accumulations of calcium-mucopolysaccharide complexes. These arteries become greatly distended and can be detected grossly because of their size and tortuosity. Acute and chronic myocardial infarct-like lesions are found but these cannot be associated with specific coronary thrombi or arteriosclerotic lesions. Valvular scarring, calcification of the papillary muscles and disappearance of myocardial mast cells has been correlated with advancing arteriosclerosis. The relation between the intensity of coronary arteriosclerosis and the frequency of breeding, the sex of the animal, and the strain indicates that the pathogenesis of this disease in breeder rats is probably governed by hormonal factors, e.g., sex and adrenal steroids, as well as by genetic factors.