Development of a lipid-rich, soft plaque in rabbits, monitored by histology and intravascular ultrasound

Lipid rich, soft plaques in the clinic are a common forerunner to occlusive thrombus formation, even with modest arterial stenosis. Animal models of a therosclerosis, obtained by various methods, do not generally allow direct in vivo evaluation of the lesion and, furthermore, cannot be examined more than once. The aim of the study was the generation of a rabbit model of ath erosclerosis, with mrphological characteristics similar to human lipid-rich , soft atheromatous plaques, and the evaluation of the reliability of intra vascular ultrasound (IVUS) technology in the study of the development of at herosclerotic lesions in this model. Briefly, New Zealand white rabbits und ergo perivasculr electrical injury at both common carotid arteries, togethe r with a 1.5% cholesterol diet for up to 90 days. The lesioned arterial seg ments show progressive changes, from diffuse cellular mortality, to macroph age infiltration in the media, up to the fil migration of macrophages to th e neointima, resulting in bulky, eccentric, macrophage and lipid-rich lesio ns. At IVUS, the produced lesions dearly resemble those described as 'soft plaques' in the clinical setting, with minimal calcification and reduced ec ho-reflectivity versus the adventitial layer. Quantitative and morphometric analysis of plaques shows a significant correlation between histological a nd IVUS measurements at each time point. In conclusion, vascular injury in the common carotids of rabbits generates atherosclerotic lipid-rich, soft p laques, that can be properly assessed by the IVUS methodology. The easy acc essibility of the arterial lesion allows serial IVUS investigations and the direct evaluation of a number of locally or generally delivered therapeuti c agents. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.