SURVIVAL AND CARDIOVASCULAR PATHOLOGY OF HETEROZYGOUS WATANABE HERITABLE HYPERLIPIDEMIC RABBITS TREATED WITH PRAVASTATIN AND PROBUCOL ON A LOW-CHOLESTEROL (0.03-PERCENT)-ENRICHED DIET

This study was aimed at determining the effects of a combined pravasta tin and probucol regimen on survival and vascular pathology of heteroz ygous Watanabe heritable hyperlipidaemic (WHHL) rabbits fed a low-chol esterol (0.03%)-enriched diet. Pravastatin monotherapy preceded the co mbined treatment. In animals receiving pravastatin and the enriched di et (verum group; n = 6), mean total serum cholesterol levels were cons istently lowered at a dosage of 5 mg/kg pravastatin and with the combi ned treatment. Survival was increased (median 45 vs 25 months), while coronary atherosclerosis was less obstructive and altered to a more fi brous 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 r evealed less severe stages with a different composition and architectu re, 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 t o a different, more stable type of atherosclerotic disease in this ani mal model.