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Restenosis after the implantation of a drug-eluting stent or after vascular irradiation therapy shares similar physiopathological mechanisms. No experimental data are currently available on vascular wall behavior after external irradiation on arteries stented with sirolimus-eluting stents (SES). Ten New Zealand white rabbits received a 0.5% cholesterol-enriched chow for 1 month. Bilateral iliac artery stent implantation was then performed with an SES (Cypher; Cordis Corp). The animals were randomized into either an irradiated group (I, 2 Gy external x-ray irradiation, n = 5) or a control group (C, n = 5). The cholesterol-enriched chow was continued for 1 additional month after stent implantation. The stented arteries were harvested for histological analyses. The number and the percentage of incompletely apposed stents struts (IASS) were significantly higher in irradiated versus control group (3.05 +/- 0.46 vs. 1.57 +/- 0.27 IASS, P < 0.01, and 28.44% +/- 3.97% vs. 15.2% +/- 2.46% of IASS, P < 0.01, respectively). The mean neointimal thickness behind the IASS was also higher in the irradiated group (I: 28.3 +/- 2.5 microm vs. C: 18.2 +/- 2.3 microm, P < 0.01). Re-endothelialization was lower in irradiated group (I: 44.6% +/- 17.5% vs. C: 75.2% +/- 5.7%, P < 0.01). The present study revealed that low-dose external irradiation increased incomplete stent apposition and reduced re-endothelialization of SES. These results underscore the potential deleterious cumulative side effects of these 2 procedures to prevent restenosis.

Structural changes that might influence the structural integrity of the vessel in response to intravascular brachytherapy (IVB) and stenting were examined, focus being on the importance of neovascularization in rabbit stented arteries. Stents were implanted in the infrarenal aortas of rabbits, immediately followed by gamma IVB or a sham radiation procedure, and the arteries harvested at 6 months. Labelling for von Willebrand factor showed an increase in adventitial and medial neovascularization in irradiated versus control arteries group (5.04+/-0.89 versus 1.51+/-0.23 mm(-2), respectively; p=0.004). Moreover, intramedial haemorrhages (free hemosiderin deposition) and inflammation (macrophages) were only observed in irradiated arteries. No significant change in expression of matrix metalloproteinase 1, 2 or 3 was observed between the irradiated and control group while collagen content decreased in the irradiated versus the control group (10.05%+/-1.48% versus 31.92%+/-3.12%, respectively; p

The effect of myocardial ischemia on nitric oxide (NO) production is controversial in part because of indirect NO quantification. In the present study, direct quantification of NO was investigated in an in vivo rat model of myocardial ischemia (MI). A NO spin-trapping technique using electron spin resonance (ESR) spectroscopy was used to study NO production in the ischemic and in the nonischemic area of the rat heart 2, 8, or 24 h after left main coronary artery ligation. The method was based on the trapping of NO by a metal-chelator complex consisting of N-methyl-D-glucamine-dithiocarbamate (MGD) and Fe(II) to form a stable NO-FeMGD complex that gives rise to a characteristic triplet ESR spectrum. This metal-chelator complex was administered half an hour before sacrifice of the rats. A large and time-dependent increase of the ESR signal corresponding to the NO-FeMGD complex was observed 8 h (11.6 +/- 0.9 arbitrary units [AU]) and 24 h (29.7 +/- 2.9 AU) in the ischemic area after MI. On the contrary, no ESR triplet was observed in the nonischemic region of the heart and in sham-operated rats. NO blood derivative levels (nitrosylhemoglobin and plasma nitrites and nitrates) were unchanged compared with sham-operated rats. Previous administration of aminoguanidine, a NO synthase inhibitor, in animals subjected to a 24-h ischemia resulted in a complete abolition in the NO-FeMGD spectrum in the ischemic area. These findings directly demonstrated an increase of the NO-FeMGD levels during in vivo myocardial ischemia that appeared to be specifically localized in the ischemic area.

To determine the nature of the changes of the vascular wall after intravascular brachytherapy in stented arteries leading to incomplete stent apposition.Stents were implanted in the infrarenal aortas of rabbits, and gamma-intravascular brachytherapy (18 Gy) or a sham radiation procedure was immediately implemented. The arteries were harvested at 6 months for histologic analyses.The external elastic lamina area, as well as the vascular wall area behind the stent, were significantly greater in irradiated vs. control arteries (8.94 +/- 0.68 mm2 vs. 6.87 +/- 0.40 mm2 [p0.001] and 1.56 +/- 0.13 mm2 vs. 0.72 +/- 0.07 mm2 [p0.001], respectively). The ratio of the intimal area behind the stent related to the total intimal area was greater in the irradiated segments (control vs. irradiated: 9.0% +/- 5.9% vs. 55.3% +/- 15.5%, p0.05). Neointimal growth of the irradiated vessels outside the stent was characterized by marked fibrin depositions and an inflammatory response around the stent struts.Our study revealed the presence of a neointimal layer specifically located behind the stent, which represented the result of an unhealed fibrin-rich tissue growth process 6 months after intravascular brachytherapy.