Development of a rabbit model of eccentric carotid atherosclerotic stenosis via localized cryoinjury.

Abstract

Background: The eccentric stenosis morphology in patients with intracranial atherosclerotic stenosis (ICAS) has a critical impact on the efficacy of endovascular treatment. This study aimed to establish a rabbit model of eccentric carotid atherosclerotic stenosis that mimics the pathophysiological and morphological characteristics of eccentric plaques in humans.

Methods: Rabbits received localized cryoinjury of the right carotid artery after 2 weeks of a high fat, high cholesterol diet, followed by an additional 8 weeks on the same diet. On the experimental endpoint, comprehensive analyses of the model's pathological changes were conducted using serum lipid analysis, DSA, optical coherence tomography (OCT), histopathological analysis, and immunohistochemistry.

Results: The high fat, high cholesterol diet significantly elevated serum lipid levels in rabbits. Hematoxylin and eosin staining results at 24 hours postoperatively revealed focal intimal damage induced by 5 s of cryoinjury. After localized cryoinjury and high fat, high cholesterol diet feeding, DSA results demonstrated significant carotid stenosis, with a stenosis degree of 47±5% and a length of approximately 9 mm. OCT images revealed eccentric fibrous plaque formation at the stenotic site. Morphological analysis of the plaque samples demonstrated a plaque eccentricity index of 0.66±0.05 and a plaque burden of 60.68±7.41%. Histopathological analysis showed that atherosclerotic lesions developed in all rabbits of the model group. Among them, three rabbits had intermediate lesions, one rabbit had atheroma, and eight rabbits had fibroatheroma.

Conclusions: This study successfully established a rabbit model of eccentric carotid atherosclerotic stenosis, providing a novel experimental platform for transformation research of neurointerventional devices.