Cholesterol kinetics in control and hypercholesterolemic foxhounds

Foxhounds were made hypercholesterolemic by thyroidectomy and cholesterol feeding. Tracer cholesterol was administered orally, and i.v. and serum samples obtained sequentially for 30 to 89 days at which time the dogs were euthanized and necropsied. Serum and selected tissues were analyzed for cholesterol radioactivity. Kinetics of cholesterol metabolism were calculated. The hypercholesterolemic dogs had large concentrations of cholesterol in the liver. The only kinetic parameter which was correlated with degree of atherosclerosis was the size of pool 2. Absorption of cholesterol was not different in the hypercholesterolemic from control dogs. Tissue cholesterol disappearance rates suggest a third pool of cholesterol having T 1/2 of greater than 200 days. The bile cholesterol kinetics suggest that cholesterol excreted was derived from the very slow pool. Excretion rate and volume appear to be the factors which are most responsible for the inability of the whole animal to maintain homeostasis in cholesterol concentration when a large amount is consumed.