METHODS: Sixteen mongrel dogs were randomized (eight animals per group) to receive either bare-
metal 1.5 x 8-mm (six-cell)
stents or
sirolimus-eluting
stents of the same dimensions. Interventionists, histopathologists, and histopathology technicians who participated in the study were blinded to the
stent characteristics.
Stents were implanted in the canine BA. Serial peripheral blood samples were obtained during the 1st week after implantation to determine the time-dependent serum concentration of
sirolimus. Follow-up angiographic studies were performed 30 days after
stent implantation to assess the effects of
stent placement on the BA and brainstem perforating vessels. Explantation of the
stent and BA was performed immediately after angiography by using a pressurized
formalin fixation procedure. Histological and computer-assisted morphometric analyses of specimens obtained in each animal were performed.
Sirolimus could not be detected in peripheral blood samples obtained later than 24 hours posttreatment. On follow-up angiography, all perforating vessels observed on initial angiograms remained patent, and no evidence of parent vessel damage or
pseudoaneurysm formation was observed. Explanted vessels and brainstem sections did not demonstrate evidence of histological neurotoxicity, such as
gliosis or
infarction. No significant differences were found in the time to endothelialization of bare-
metal and
sirolimus-coated
stents. Smooth-muscle cell (SMC) proliferation, the putative agent for restenosis, was lower in animals receiving
sirolimus-coated
stents (p = 0.003). Additionally, intimal
fibrin density was increased in the dogs treated with
sirolimus-coated
stents (p < 0.0001). Histological evidence of an inflammatory response demonstrated a trend toward a reduced response in the
sirolimus group (mean 0.58) compared with the bare-
metal group (mean 0.83, p = 0.33).
CONCLUSIONS: No neurotoxic effects were observed in the intracranial vessel walls or brainstem tissue in which
sirolimus-coated
stents were implanted. Compared with bare-
metal stents, the
sirolimus-coated devices did not impair endothelialization and, furthermore, tended to reduce the proliferation of SMCs. These findings indicate that
sirolimus-coated devices may inhibit in-
stent stenosis. Further studies with longer-term follow up are required to assess the restenosis rates of
sirolimus-coated
stents implanted in the intracranial vasculature.