Effect of calcification on in vivo mechanical response of rabbit arteries to balloon dilation

Abstract

Background: Atherosclerosis has been associated with loss of artery wall distensibility in human cadavers and in experimental animal models, giving it the lay term "hardening of the arteries."

Methods and results: To assess the effect of calcification on arterial distensibility, balloon pressure and volume were recorded during dilation of calcified aortas in Watanabe heritable hyperlipidemic (WHHL) rabbits in vivo. Calcification was induced by dietary supplements of cholesterol, vitamin D2, and calcium. Balloon pressure, volume, and time signals were acquired at high frequency with controls for temperature and balloon inflation rate. Resistance to balloon dilation was minimal in control rabbit aortas (delta Vmax = 5.0 +/- 3.5 microliters) and in excised nonatherosclerotic human coronary arteries, and it was small in aortas from cholesterol-fed rabbits (12.3 +/- 8 microliters), even when lipid levels were markedly elevated by a high cholesterol diet (611 +/- 347 mg/dl). With dietary cholesterol, vitamin D2, and calcium supplements, WHHL rabbits developed mild hypercalcemia (15 +/- 1.9 mg/dl), hypercholesterolemia (1,100 +/- 633 mg/dl), moderate-to-marked aortic calcification, and high resistance to balloon dilation (38 +/- 27) comparable to that seen in angioplasty patients.

Conclusions: It is concluded that experimentally induced calcification decreases the distensibility of the rabbit aorta in vivo and that it yields to balloon dilation by plastic deformation closely resembling that seen in balloon angioplasty of human coronary arteries. These findings suggest that calcification contributes to arterial "hardening" associated with atherosclerosis.