Within the past few years many workers have attempted by various means, to produce arterial lesions in animals, chiefly rabbits and dogs. The present status is somewhat chaotic, some affirming and some denying that arterial changes follow the various methods employed. Following the injection of small, repeated doses of adrenalin over a certain period of time, changes occur in the arteries of rabbits which are arteriosclerotic in type, the essential lesion being a degeneration of the muscular and elastic tissue of the media with the consequent production of aneurysm in the vessel. This is said by some to be quite like the type of arteriosclerosis in man which has been so well described by Moenckeberg. The degenerations in the arteries following the experimental lesions are of the nature of a fatty metamorphosis, and later proceed to calcification. Barium chloride, digitalin, physostigmin, nicotin and other substances, as well as adrenalin, have been found to exert a selective toxic action on the muscle cells of the middle coat of the aorta. The infundibular portion of the pituitary body, the portion which is developed from the infundibulum of the brain, possesses an internal secretion, which, injected intravenously, causes a marked rise of blood pressure and slowing of the heart beat. So far as I know, this active principle of the gland has not been used in an attempt to produce experimentally the lesions of arteriosclerosis.
Wacker and Hueck succeeded in producing aortic disease in rabbits which they considered to be in many points quite like human arteriosclerosis. They injected the rabbits intravenously with cholesterin. They feel that this is of great importance in view of the fact that exercise (muscle metabolism) dyspnea, certain poisons, as well as adrenalin, and even adrenal extirpation occasion a high cholesterin content of the blood. Anitschow's experiments are confirmatory. He fed rabbits on large amounts of cholesterin-containing substances (yolk of egg, brain tissue) and pure cholesterin and found changes in the intima and inner portion of the media consisting of fatty infiltration between the muscle and elastic fibres, advent of small round cells and large phagocytic cells containing fat droplets of cholesterin esters. The elastic fibres were dissolved, broken up into fibrillæ and these seemed to be absorbed. The internal elastic lamina as such disappeared and the inner layer of the aorta fused with the middle coat. He considers these changes to be quite analogous to those found in human aortas.
Oswald Loeb produced changes in the arteries of rabbits by feeding them sodium lactate (lactic acid). His controls fed on other acids became cachectic, but showed no arterial changes. He further found that in 100 gm. of human blood there was normally from 15 to 30 mg. of lactic acid. After heavy work, he found as much as 150 gm. He considers that after adrenalin or nicotin injections, the function of the liver is so disturbed that lactic acid is not bound. The arteriosclerosis is actually due to the presence of free lactic acid in the circulation. He succeeded, also, in producing lesions of the intima in a dog fed for a long time on protein poor diet, plus lactic acid and sodium lactate.
Another investigator, Steinbiss, fed rabbits on animal proteins only, a diet totally foreign to their natural habits. He succeeded, however, in keeping some alive for three months. He also tried various substances and in the general conclusions says that no aortic changes could be produced in animals kept in natural living conditions by any mechanical means, increase of blood pressure, digital compression, hanging by hind legs, etc. In infectious diseases, especially septic, widespread sclerotic changes occurred in the aorta. A most suggestive conclusion in this "the most important result of feeding rabbits with animal proteins is, along with a constant glycosuria, disease of the aorta and peripheral arteries which is identical with changes in the aorta produced by injections of adrenalin. The degree of disease of the circulatory system increases with the duration of the experiment."
By a small addition of vegetable to the protein diet, the lives of the animals were prolonged at will. With this modification of the experiment, the findings in the vessel walls were noticeably altered. The changes affected chiefly the intima, to less degree the media, and histologically were very much like human intimal disease.
I have been unable to produce the slightest arterial lesions in rabbits by intravenous injections of lead. Frothingham had no success feeding animals with lead. In a study of autopsy material from persons up to 40 years, who died of infectious disease, he found changes in the arteries of those who had succumbed to infection with the pus cocci or to very severe infectious disease. These changes were, however, localized, and were not like those of the general diffuse arteriosclerosis.
Adler has recently reported experiments on dogs, to which he fed or injected intravenously various substances supposed to induce arteriosclerotic changes. He was unable to find any arterial lesions comparable to human arteriosclerosis.
The difficulty experienced by experimenters is not surprising when the character of the changes is considered. Arteriosclerosis is not an acute process. In its very nature, it is of months' or years' standing, the specific changes are of slow growth, and more in the nature of degeneration. It would seem that a very careful study of the histories of those with arteriosclerosis and a final examination upon the actual tissue might eventually give us data for the etiology.
The most frequent site of disease in these experimental lesions is the thoracic aorta, and it is there also that the most severe changes are seen. While the toxic action is felt in the vessels all over the body, the lesions are, as a rule, scattered and small. The thoracic aorta stands the brunt of the high pressure, and this combined with the poisonous action of the drug or drugs, results in the formation of a fusiform aneurysmal dilatation which stops at the diaphragmatic opening. The aortic opening in the diaphragm seems to act as a flood gate, allowing only a certain amount of blood to flow through, and thus the abdominal aorta is protected to a great extent from the deleterious effects of increased pressure. Focal degenerative lesions are, however, found in the abdominal aorta.
Changes somewhat analogous to those found in the human aorta as the result of intimal proliferations, are produced in animals by the toxins of the typhoid bacillus and the Streptococcus pyogenes. Clinically, Thayer and Brush have found that the arteries of those who have recovered from an attack of typhoid fever are more palpable than the arteries of average individuals of equal age who have never had the disease.