In vivo model of intracranial stent implantation: a pilot study to examine the histological response of cerebral vessels after randomized implantation of heparin-coated and uncoated endoluminal stents in a blinded fashion

Abstract

Object. No animal model currently exists for the examination of time-dependent histological changes occurring in intracranial vessels after endoluminal stent placement. The authors' goal was to develop a reproducible in vivo model of stent implantation in intracranial vessels in dogs that was capable of demonstrating stent-related vascular changes after the implantation of coated and uncoated devices. Methods. The authors implanted heparin-coated or uncoated stents in the basilar arteries (BAs) of 11 mongrel dogs. In a 12th animal, one coated stent was implanted in the BA and a second uncoated one was implanted in the distal anterior spinal artery. All the devices were oversized to induce intimal injury. Surviving animals were observed for 12 weeks, after which they underwent repeated angiography before planned death and removal of the brain. Histological studies and computer-assisted morphometric analyses were conducted on stent-treated and untreated sections of the BAs to assess the percentage of stenosis, neointimal proliferation, vessel injury, and inflammation. Perforating vessels partially covered by stent struts (“jailing”) were studied for evidence of stenosis or occlusion. The pathologist, interventionists, histopathologist, histopathology technicians, and radiologist were blinded to the stent type. Seven stents (three uncoated and four coated) were removed from the six animals that were observed during the follow-up period. The mean neointimal proliferation was 0.42 mm2 in the group treated with uncoated stents and 0.18 mm2 in the group treated with heparin-coated devices (p = 0.04). Neointimal thickness was significantly increased in the group with uncoated stents (p = 0.04). The mean percentage of occlusion was less (12%) in the group with heparin-coated stents, compared with 22% in the group with uncoated devices (p = 0.07). When comparing results between the heparin-coated and uncoated devices implanted in the five animals that received a single stent only, greater differences (indicating a benefit from heparin-coated stents) were observed in neointimal area (p = 0.009), neointima/media ratio (p = 0.001), neointimal thickness (p = 0.002), and percentage of occlusion (p = 0.009). All brainstem perforating vessels covered by stent struts remained patent. Conclusions. This in vivo intracranial stent model was developed to assess proliferative and inflammatory responses to endoluminal stent implantation in the cerebrovasculature. The results indicate that a lower percentage of occlusion occurs 12 weeks after implantation of heparin-coated compared with uncoated stents.