Abstract
Dragstedt, Van Prohaska and Harms 1 reported observations on a substance present in pancreas which permits survival and prevents liver changes in depancreatized dogs. To this substance they gave the name “Lipocaic”. The interesting effects of this substance on lipoid metabolism led us to investigate its effect on the atherosclerosis which can be produced in rabbits by feeding cholesterol and foods high in cholesterol content. This experimental vascular change in rabbits has been studied particularly by Anitschkow, 2 Bailey, 3 Clark-son, 4 Dominguez, 5 and Duff. 6 Lipocaic was prepared according to the method of Dragstedt, Van Prohaska and Harms. 1 The procedure involves the extraction of fresh pancreas with 60% ethyl alcohol. The alcohol extract is then evaporated at a temperature less than 40°C. The residue is extracted with sulphuric ether. The fat-free extract dissolved in water was so diluted that 5 cc. contained the extract of 50 gm. of pancreas.
In this study, the diet fed to all the rabbits consisted of a standard ration of oats, Purina rabbit chow and green vegetables. Each rabbit receiving the high cholesterol diet was given each morning one 50 cc. beaker of this chow containing 0.5 gm. cholesterol and one-half egg yolk. No difficulty was experienced in making the animals eat this mixture. After eating this, they were given additional food.
In the case of the hormone, the preparation of which was described above, 5.0 cc. of the concentrated watery substance containing the extract obtained from 50 gm. of pancreas was added to a 50 cc. beaker of Purina rabbit chow. Each rabbit receiving the hormone was given one of these beakers of chow daily.
All animals used in this experiment were approximately 6 months of age at the beginning of the experiment. Rabbits Nos. 3, 6, and 13 were from one litter, and Nos. 11, 12, and 16 from another litter.
The procedures carried out in the six groups of rabbits are described in Table I.
Weekly determinations of blood cholesterol were done according to a modification of the method of Bloor. 7
The feeding experiment continued for 10 weeks after which Rabbits 1, 2, 4, 5, 7, 8, 10, 11, 14, and 15 were sacrificed and an autopsy done. Rabbits 3, 6, 9, 12, 13, and 16 were observed for a period of 20 weeks and then sacrificed and an autopsy done. Gross and microscopic studies were made of the vascular system and organs of all animals.
The effects of the administration of lipocaic are evident both in the changes in blood cholesterol and in the gross and microscopic appearance of the aorta of the rabbits at an autopsy.
The results are shown in Table I. The blood cholesterol changes in the first 4 groups of animals are graphically illustrated in Chart 1. The microscopic appearance of the aorta of the experimental animals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, and 16 is shown in Chart 2.
Lipocaic does not affect the level of blood cholesterol in normal animals. It prevents the rise in blood cholesterol and the development of atherosclerosis in the aorta which otherwise regularly occurs in rabbits fed a high cholesterol diet. Heated hormone is ineffective.
Studies are in progress concerning the use of lipocaic in the treatment of atherosclerosis in rabbits in whom the condition has been allowed to develop. The resemblance of cholesterol atherosclerosis of rabbits to the pathology of sclerotic vascular disease in man suggests the possibility of the use of this pancreatic extract in the prevention and treatment of human atherosclerosis.
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