Survival and cardiovascular pathology of heterozygous Watanabe heritable hyperlipidaemic rabbits treated with pravastatin and probucol on a low-cholesterol (0.03%)-enriched diet

Abstract

 This study was aimed at determining the effects of a combined pravastatin and probucol regimen on survival and vascular pathology of heterozygous Wa- tanabe heritable hyperlipidaemic (WHHL) rabbits fed a low-cholesterol (0.03%)-enriched diet. Pravastatin monotherapy preceded the combined treatment. In animals receiving pravastatin and the enriched diet (verum group; n = 6), mean total serum cholesterol levels were consistently lowered at a dosage of 5 mg/kg pravastatin and with the combined treatment. Survival was increased (median 45 vs 25 months), while coronary atherosclerosis was less obstructive and altered to a more fibrous type than in controls (n = 8). The extent of aortic lesions, as determined by the relative plaque volume, was not related to survival in either group. However, aortic plaque types in verum group animals revealed less severe stages with a different composition and architecture, with a lower relative content of macrophage-derived foam cells and necrosis and a higher relative content of extracellular matrix. There was also a thicker fibrous cap than in control animals of similar age. Our data reveal a beneficial effect on survival of heterozygous WHHL rabbits when lipid-lowering and antioxidative treatment are combined. This appears to be due both to reduced coronary atherosclerosis and to a different, more stable type of atherosclerotic disease in this animal model.