Observations Concerning the Production and Excretion of Cholesterol in Mammals

Investigators (l-6) are agreed that in man, the dog, and the rat biliary obstruction is followed by a rise in the total cholesterol concentration of the blood.Opinion is not uniform concerning the changes in blood content of esterified cholesterol after biliary obstruction.Thus, Epstein and Greenspan (3,4) observed a rise in cholesterol ester concentration of the blood in the majority of their patients who suffered from obstructive jaundice, whereas Man et al. ( 6) observed a reduction in the concentration of esterified cholesterol in a group of similar patients.Chanutin and Ludewig (5) found, at most, slight change in the esterified cholesterol content of the plasma of rats subjected to ligation of the bile duct.The mechanism responsible for the rise in the free cholesterol content of blood plasma following biliary obstruction is not clear.It was felt that further information concerning this mechanism, and concerning the formation of esterified cholesterol, might be gained if animals with ligated bile ducts were subjected to an acute additional cholesterol load.The latter was accomplished by the intravenous injection of a specially prepared suspension of free cholesterol stabilized with sodium laurate (7). MethodsMale and female rats (albino and Long-Evans strains), weighing between 140 and 200 gm., were used.One series of 50 rats was operated upon under ether anesthesia and the bile duct ligated.Blood samples (1 ml.) were obtained 6, 24, and 72 hours after ligation and the plasma was analyzed for free and total cholesterol.A control series of twelve rats was anesthetized, the abdominal cavity opened, and the bile duct manipulated in a laparotomy.Blood samples were obtained and the plasma analyzed exactly as in the larger group.A series of twenty-six rats was operated upon as above, the bile duct ligated, and immediately after ligation the rats were given, by intravenous injection, a suspension of 2.6 per cent free cholesterol prepared as reported