In this study, young growing swine were made hypercholesterolemic (~300 mg/dl) by feeding milk and eggs for 7 wk. They were then divided into three groups (untreated, clofibrate-treated, and cholestyramine-treated), and the diet was continued for an additional 3-4 wk. A cholesterol balance study was carried out in the terminal week. When the swine were killed, the total carcass content of cholesterol was determined, as well as contents of individual tissues. Both drugs caused a 50% reduction in serum cholesterol levels. The total carcass cholesterol contents were significantly lower in both treatment groups than in the untreated group. The difference was due largely to lower concentrations in the plasma and in bulk tissues. [4-(14)C] Cholesterol was fed 7 days before the animals were killed, and specific activities of cholesterol in individual tissues were determined terminally. These gave a broad spectrum of values in tissues (excluding central nervous system) ranging rather evenly from 33% of plasma specific activity in the aorta to 100% in some tissues. The balance data suggest that cholestyramine reduces the enterohepatic bile acid pool and cholesterol absorption but increases fecal output of bile acids and total body cholesterol synthesis. The balance data, limited to the terminal week, give no indication of the mode of action of clofibrate. Even synthesis was not significantly lower than in the untreated swine.

Animals↗

PubMed1973

Population dynamics of arterial smooth-muscle cells. II. In vivo inhibition of entry into mitosis of swine arterial smooth-muscle cells by aortic tissue extracts.

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Animals↗

PubMed1972

Cholesterol turnover, synthesis, and retention in hypercholesterolemic growing swine.

Studies of the interaction of cholesterol absorption, excretion, synthesis, and retention were carried out with growing swine through the application of sterol and isotopic balance procedures to a non-steady state situation. The animals were fed either a low-fat commercial mash diet (MA), a commercial mash diet plus 2.4 g/day of crystalline cholesterol (MAC), or a high-fat milk diet containing 2.4 g/day cholesterol (MKC). [(14)C]Cholesterol and beta-[(3)H]sitosterol were used to measure fecal neutral steroid losses. Final plasma cholesterol levels averaged 91, 85, and 195 mg/100 ml for MA, MAC, and MKC animals, respectively. Total carcass dissection followed by cholesterol measurement revealed that accumulation of cholesterol in most body tissues was directly related to increase in body size in the rapidly growing swine. The only notable exceptions were plasma, liver, and bone with marrow of the MKC group, where cholesterol concentrations were significantly elevated. Absorption of cholesterol was significantly greater in animals fed MKC than MAC-fed swine (726 mg/day vs. 142 mg/day), whereas synthesis of cholesterol was significantly greater in MAC animals than in MKC animals (863 mg/day vs. 112 mg/day). Excretion of neutral and acid steroids into the intestine was not significantly different between MAC and MKC groups, but both classes of steroids were more efficiently reabsorbed in MKC animals. The overall differences between swine fed mash-cholesterol and those fed milk-cholesterol diets appear to result from more efficient absorption of both neutral and acid steroids in the milk-cholesterol group only partially compensated for by decreased cholesterol synthesis.

Animals↗

PubMed1971