Decreased coronary vascular reserve in Watanabe heritable hyperlipidemic rabbits

Watanabe heritable hyperlipidemic (WHHL) rabbits have severe hypercholesterolemia due to a genetic defect in their low density lipoprotein receptors. Therefore, they develop severe premature atherosclerosis of the large arteries including the coronary arteries. In the present study, we measured the coronary vascular reserve of these rabbits to evaluate the total cross-sectional coronary surface area. This method allowed us to quantify the functional consequences of the coronary atherosclerotic lesions. To evaluate coronary vascular reserve, we measured coronary blood flow with the radioactive microsphere technique before and after induction of maximal coronary vasodilation by an intravenous dose of 9 mg/kg of carbocromen. A group of pure-bred WHHL rabbits was compared to a group of normal Burgundy rabbits at ages of 100 and 300 days. At 100 days, there was no difference in coronary vascular reserve between the two groups. However, at 300 days, the coronary vascular reserve in WHHL rabbits was 48% smaller than in the normal Burgundy rabbits (p less than 0.001). In addition, by making corrosion casts and morphological studies, we were able to show that at 300 days nearly all the WHHL rabbits had severe coronary atherosclerotic lesions located mainly at the origin of the large coronary arteries. We conclude that WHHL rabbits at 300 days have a severe impairment of their coronary vascular reserve due to proximal atherosclerotic lesions in the coronary arteries.