No abstract

Ignatovski (1) in 1908 published the results of his experiments on the effect of animal food on the rabbit. By feeding milk and egg yolk to these animals he produced various lesions, the most noteworthy of which were atheroma of the aorta, cirrhosis of the liver, and enlargement of the adrenals. In the following year Starokadomsky and Ssobolew (2), also by feeding rabbits on milk and egg, confirmed the results of Ignatovski in so far as the production of an atheroma of the aorta was concerned. They also obtained lesions in the innominate artery, carotids, and subclavians. Ignatovski ascribed his results to animal proteids. Several workers had previously described lesions produced in rabbits by animal food (d'Amato (3) lesions of the aorta, and Gamier and Simon (4) lesions of the liver), but these lesions differed essentially from those produced by Ignatovski and the latter's results attracted particular attention on account of the similarity of the aortic lesions as described by him to human atheroma. Stuckey (5) also confirmed Ignatovski's results. He afterward attempted to determine what part of the food given was responsible for the lesions, trying (6) milk, meat juice, egg albumin, and egg yolk, with the result that lesions as described by Ignatovski were produced only by the egg yolk. Later (7) he used different animal and plant fats, fish liver oil, beef ;fat, and sunflower-seed oil with negative results. He did, however, produce lesions of the aorta, apparently identical with those described by Ignatovski, by feeding rabbits on brain.Chalatow (8) studied the livers of Stuckey's rabbits and reported characteristic changes in the livers of those which had been fed on egg and brain. In these he found an abundant infiltration of the parenchyma with doubly refracting fat.Wesselkin (9) fed rabbits on egg and milk and others on lecithin and milk. In the former he obtained an abundant deposit in the liver, aorta, and spleen of lipoid substances which he considered mainly cholesterol esters. In the lecithinfed rabbits also he found in the same organs a deposit of lipoids which, from their mlcrochemical reactions, he believed to be phosphatids. Because, however, no pathological changes followed the deposit of the latter in the organs, while marked changes were produced by the cholesterol esters, he concluded that the injury was to be ascribed to the cholesterol of the egg yolk. 69 on

The repeated intravenous injection of rabbits with living Bacillus coli communior over long periods has resulted in the formation of amyloid deposits in the spleen, liver, and kidneys. Suppurative lesions were not present in most cases and therefore not a factor in its production. The results have been constant in that amyloid was found in all rabbits, eight in number, which were injected over a period of 88 days or more. Eight rabbits showed amyloid in the spleen, six of these in the kidneys also, and three in the liver. The kidneys of these eight rabbits also showed as a result of the injections a subacute and chronic glomerulitis, parenchymatous degeneration, some interstitial infiltration with round cells, and a slight cellular proliferation of connective tissue, thus resembling the chronic parenchymatous nephritis of man which is so commonly associated with amyloid disease.

The following experiments were done to test the possibility of the production of atheroma of the aorta in guinea pigs by cholesterol feeding, and also to test certain theories which have been advanced as to the importance of factors, other than the cholesterol, in the production of this type of atheroma.Four guinea pigs were fed on daily doses of 0.1 to 0.5 gm. of cholesterol dissolved in cotton seed oil for periods of 18 to 72 days. These animals, like rabbits similarly fed, show an enlargement of the adrenals, and an abundant deposit of anisotropic fat in the liver and spleen, the situation of this fat being similar to that previously described in these organs in the rabbit. An occasional guinea pig in this and the following experiments showed focal areas of degeneration in the cortex of the adrenal with a deposit of calcium. The aortas show no gross lesions. Microscopically there are found small patches of fatty infiltration in the intima and upper media. The characteristic proliferation and subsequent degeneration seen in the rabbit were entirely lacking. The feeding periods were too short to conclude that such tissue reaction might not ultimately result. One guinea pig which received 20 g. of cholesterol in 72 days (15.1 g. in the last 40 days) would seem however quite comparable with a rabbit, previously reported, which showed pronounced atheroma after receiving 13.7 g. in 37 days. From these experiments and others which follow it can at least be concluded that a longer period and larger doses are necessary for the production of an atheroma in the guinea pig than in the rabbit.

There may be produced in rabbits by the intravenous injection of large doses of diphtheria toxin a vascular degeneration involving the entire aorta, the carotids to the base of the skull, the subclavians, and iliacs, and, for a varying distance distally, the brachials, femorals, and large abdominal vessels. The first part of the pulmonary artery is sometimes affected. The lesion is practically diffuse throughout the aorta and vessels mentioned, consisting of a fatty degeneration and necrosis of the smooth muscle in a wide zone of the media and a crowding together of the elastic fibers in the region affected, resulting in an irregular thinning of the vessel walls and many small aneurysmal pouchings. In rabbits which received pituitrin with the diphtheria toxin extensive calcification occurred throughout this degenerated zone, both in the aorta and other large vessels. It is believed, however, that pituitrin is not essential to the calcification and that if it is of any importance it is because an extreme fatty degeneration is produced more quickly in the media of the vessels when it is administered simultaneously with the toxin. Diphtheria toxin, given in large doses intravenously, produces in the kidneys of the rabbit a pronounced vascular and parenchymatous degeneration. The former consists of a swelling and desquamation of the endothelial cells of the arterioles and small veins with the formation of fibrinous thrombi, a necrosis and thrombosis of the capillaries of the tufts with hemorrhage and the formation of fibrinous and hyaline masses, and in some of the affected glomeruli considerable collections of polymorphonuclear leukocytes.