Experimental Studies on Coronary Atherosclerosis

Abstract

Experimental cholesterol atherosclerosis is now widely utilized for the study of human atherosclerosis, and in some points is considered as a model of the human disease. But from another point of view, there are certain differences found between the experimental and human diseases. The following facts are well recognized as the main differences : (1) In experimental atherosclerosis, the arterial lesions mostly consist of foam cell plaques containing enormously large amounts of lipids, and are combined with hyperlipemia and general organ and tissue lipid deposition. In the human disease, however, no such constant and marked organ lipid deposition or hyperlipemia are seen and the arterial lesion contains more fibrotic, hyalinized or calcified areas. (2) In the experimental disease, no necrosis, hemorrhage, ulcer or thrombus-formation of the focus can be induced and thus such organ injury as myocardial infarction or encephalomatacia can seldom be induced.From the clinical point of view, the most important process of the pathology is the occlusion of the vessel lumen and the following ishemic injury of the organs, especially that of the heart and the brain. However most of the experimental studies on atherogenesis are focused upon the aortic atherogenesis, and there are but few reports on experimental coronary atherosclerosis and its following heart diseases.Therefore, the author has taken up the experimental production of coronary sclerosis and resultant coronary heart diseases in the rabbit, and carried out comparative studies of these rabbit-materials with those of human lesions. In the latter part of the paper, the action of some anti-atherogenic substances and the experimental methods for the screening of these drugs are discussed.(1) Coronary atherosclerosis in the rabbit along with aortic disease induced by a long term lanolin feeding in the animal, and the resultant stenosis or occlusion of the vessels caused the coronary heart disease, were similar to such lesions as acute myocardial infarction or chronic myocardial fibrosis in humans.(2) The combined use of vascular injury by allylamine or sodium chloride treatment, or of reticuloendothelial disturbances through India ink or trypan blue administration along with the lanolin feeding, precipitated the coronary and aortic atherogenesis.(3) In experimental cholesterol atherosclerosis, the fibrotic, hyalinizing or calcifying tendencies of the lesion and the occlusion of the vessel lumen, may be produced as the pathologic progress just like as in human atherosclerosis. And further as a resultant of these changes, organ parencymal lesions may likely be produced.(4) In the experimental cholesterol atherosclerosis, the mucopolysaccharide changes in the vessel ground substance were seen to precede the intimal fat deposition, equally like as in the human pathology. The changes of mucopolysaccharides, however, may represent a sort of vascular injury which occurs in many vascular disease other than atheromatosis, and the fact can not support any opposing opinion to the lipid theory of atherogenesis.(5) Chondroitin sulfate, α-phenyl-N-butyryl taurine salt, α-phenyl-N butyryl-d-glucosamine or estradiol benzoate seemed to be effective on lowering the plasma cholesterol level and inhibiting atherogenesis.(6) As a screening method for anti-atherogenic drugs through a plasma cholesterol lowering action, the administration of the drug can be terminated in 6 to 9 weeks of experimental feeding and the final plasma cholesterol value can be evaluated as an indicator of their effects.(7) As a method for comparing the degree of aortic atherosclerosis, the estimation of the aortic cholesterol content is valuable, so far as the lesions are not in a too advanced stage, because the method offers the statistical treatment of the data.I wish to offer the thanks to Prof. Imasato Donomae for his continuous guidance.