Abstract
Purpose: Although various types of stents have been used to treat symptomatic intracranial stenosis, how stents interact with atherosclerotic plaques has not been evaluated. In this study, we demonstrate the utility of a swine carotid atherosclerotic model for the preclinical evaluation of intracranial stenting therapies. Methods: Advanced atherosclerotic plaques were induced in 28 carotid arteries of 14 Chinese miniswines using partial ligation and high cholesterol diet to create >70% stenosis. The plaques were characterized with three-dimensional rotational angiography, Doppler ultrasonography, MR scan and 18F-FDG PET/CT scans at three months and correlated with histopathological examination in 20 carotid arteries. Five Wingspan stents and one Paclitaxel-eluting balloon-mounted coronary stent were implanted into six diseased vessels. Two contralateral carotid arteries were used as controls. Dual-antiplatelet regimen with clopidogrel and aspirin was administrated 1 day prior to stenting and continued for 1 month. Stent and plaque interaction was evaluated with angiography, MR scan and 18F-FDG PET/CT scans at one month after stenting. Results: The diameter of proximal and distal segments of carotid arteries were 3.6±0.1 mm and 3.8±0.1 mm at post-ligation, and 3.6±0.1 mm and 3.7±0.1 mm at 3 months, respectively, similar to that of middle cerebral arteries in human (2.7-4.9 mm, average 3.7mm). Doppler waveforms showed features of low resistant vessels. Plaque rupture and distal embolism were observed, mimicking the mechanisms of stroke in human intracranial atherosclerosis. All stents were patent at one month but 25% restenosis was observed. Wingspan stents expanded beyond the arterial lumen whereas the coronary stent stayed in the intima. Conclusion: This swine model is suitable for the testing of devices for the endovascular treatment of intracranial atherosclerosis. It can be a useful tool for the study of mechanisms of in-stent restenosis.
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