Characterization of aortic lesions in two hypercholesterolemic rabbit models and their potential application to assessing the safety of endovascular devices

Abstract

The principle shortcomings of animal models routinely used for the preclinical safety assessment of endovascular systems has been the absence of vascular pathology (atherosclerosis) and thus the ability to accurately assess the healing and vascular response of diseased arteries following device implantation. The objective of this investigation was to develop and characterize a rabbit model of atherosclerosis appropriate for testing the safety and potential efficacy of endovascular devices designed for the management of complex atherosclerotic lesions in human coronary arteries. Two groups of rabbits were used for this study, with one group receiving a 2- month-pulsed, 1.0% cholesterol diet and the other group receiving a continuous 0.3% cholesterol diet. Three rabbits from each diet group were scheduled to be euthanized at 2, 4, 6, and 9 months. From each rabbit, the length of the aorta was collected and evaluated histologically at segments along its length to assess and compare the development and character of atherosclerotic-like lesions. Results of the study show that there is little difference in either the development or character of lesions between the two dietary protocols investigated. However, rabbits on the 0.3% diet could be better maintained per protocol for the duration of the study and thus were more apt to develop atherosclerotic-like lesions. Per human classification schemes for atherosclerotic lesions, lesions that develop in the aorta in hypercholesterolemic rabbits did not progress beyond “preatheromas” or Type III lesions within the time course of this study. Inferences from and the applicability of this model to assessing the preclinical safety of endovascular devices are discussed. Guidant Corporation, Vascular Intervention, Santa Clara, CA