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The effect of 3-hydroxy-3-methylglutaric acid (HMG) on serum cholesterol levels was investigated in Watanabe heritable hyperlipidaemic (WHHL) rabbits. Oral administration of HMG resulted in a reduction of serum cholesterol by 39%. Bile acid drainage, by means of either cholestyramine medication or partial ileal bypass (PIB) surgery, also led to significant reductions in circulating cholesterol, by 35 and 59% respectively. Intraperitoneal injection of HMG after PIB surgery further reduced serum cholesterol by 35%. Fibroblasts from the WHHL rabbits did not show high-affinity binding, uptake or degradation of 125I-labelled low density lipoprotein (LDL). The working mechanism of these lipid-lowering lowering therapies in WHHL rabbits is discussed in relation to recent literature. The significant reductions in circulating cholesterol induced by HMG warrant further investigation into the use of this compound in the management of familial hypercholesterolaemia.

The effects of bile acid drainage on serum cholesterol levels have been investigated in Watanabe heritable hyperlipidemic rabbits, a unique model for homozygous familial hypercholesterolemia. Cholestyramine medication lowered serum cholesterol concentrations with 38%, while a 33% and a 50% small bowel bypass resulted in a decrease of 56 and 48%, respectively. Cholestyramine treatment after either bypass induced a minor additional fall in serum cholesterol. Ileal bypass and ileal resection were equally effective in reducing serum cholesterol. These results indicate the necessity for further investigation into the potential of bile acid drainage as a therapy in homozygous familial hypercholesterolemia.