Animal Model That Mimics Atherosclerotic Plaque Rupture

From the Department of Vascular and Cardiac Diseases, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company (M.D.R., G.W.H., D.W.B., D.G., J.A.K., M.J.R.), and the Department of Pathology, University of Michigan (C.W.W., J.-S.K, D.G.), Ann Arbor, Mich.

Correspondence to Dr Mark D. Rekhter, Vascular and Cardiac Diseases, Parke-Davis Pharmaceutical Research Division, 2800 Plymouth Rd, Ann Arbor, MI 48105. E-mail REKHTEM{at}aa.wl.com

Abstract—Atherosclerotic plaque rupture is the main cause of coronary thrombosis and myocardial infarcts. Currently, there is no animal model of plaque disruption. We have developed a rabbit model in which an atherosclerotic plaque can be ruptured at will after an inflatable balloon becomes embedded into the plaque. Furthermore, the pressure needed to inflate the plaque-covered balloon may be an index of overall plaque mechanical strength. The thoracic aorta of hypercholesterolemic rabbits underwent mechanical removal of endothelial cells, and then a specially designed balloon catheter was introduced into the lumen of the thoracic aorta. As early as 1 month after catheter placement, atherosclerotic plaque formed around the indwelling balloon. The plaques were reminiscent of human atherosclerotic lesions, in terms of cellular composition, patterns of lipid accumulation, and growth characteristics. Intraplaque balloons were inflated both ex vivo and in vivo, leading to plaque fissuring. The ex vivo strategy is designed to measure the mechanical strength of the surrounding plaque, while the in vivo scenario permits an analysis of the plaque rupture consequences, eg, thrombosis. In addition, our model allows local delivery of various substances into the plaque. The model can be used to study the pathogenesis of plaque instability and to design plaque stabilization therapy.

Key Words: atherosclerosis • catheter • plaque • rupture • thrombus

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