Inhibition of neointimal proliferation with low-dose irradiation from a β-particle-emitting stent

John R. Laird, Andrew J. Carter, William M. Kufs, Timothy G. Hoopes, Andrew Farb, Sepideh H. Nott, Robert E. Fischell, David R. Fischell, Renu Virmani, Tim A. Fischell

Research output: Contribution to journalArticle

142 Scopus citations

Abstract

Background: Restenosis after successful percutaneous transluminal coronary angioplasty is the major factor limiting the long-term effectiveness of this procedure. Neointimal proliferation in response to arterial injury is an important contributor to restenosis. The use of radiation for the treatment of malignant and benign proliferative conditions has been well established. External beam irradiation and endovascular irradiation by use of an after- loading technique have been shown to inhibit neointimal proliferation in experimental models of restenosis. The objective of this study was to investigate whether low-dose irradiation from a β-particle-emitting stent would inhibit neointimal proliferation after placement in porcine iliac arteries. Methods and Results: Fourteen titanium-mesh stents were implanted in the iliac arteries of nine NIH miniature swine. There were seven β- particle-emitting radioisotope stents (32P, activity level 0.14 μCi) and seven control stents (31P, nonradioactive). Treatment effect was assessed by angiography and histomorphological examination of the stented iliac segments 28 days after implantation. There was a significant reduction in neointimal area (1.76±0.37 mm2 versus 2.81±1.22 mm2, P=.05) and percent area stenosis (24.6±2.9% versus 36.0±10.7%, P=.02) within the β-particle- emitting stents compared with the control stents. Neointimal thickness, which was assessed at each wire site, was also significantly less within the treatment stents (0.26±0.04 mm versus 0.38±0.10 mm, P=.012). Scanning electron microscopy was performed on sections from four stents. This demonstrated endothelialization of both the treatment and control stents. There was no excess inflammatory reaction or fibrosis in the media, adventitia, or perivascular space of vessels treated with the β-particle- emitting stent compared with control vessels. At 28 days, there was no difference in smooth muscle cell proliferation as measured by the proliferating cell nuclear antigen index. Conclusions A local, continuous source of low-dose endovascular irradiation via a β-particle-emitting stent inhibits neointimal formation in porcine arteries. This low dose of local irradiation did not prevent endothelialization of the stents. This novel technique offers promise for the prevention of restenosis and warrants further investigation.

Original languageEnglish (US)
Pages (from-to)529-536
Number of pages8
JournalCirculation
Volume93
Issue number3
StatePublished - Feb 1 1996
Externally publishedYes

Keywords

  • β-particle
  • radiation
  • restenosis
  • stents

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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    Laird, J. R., Carter, A. J., Kufs, W. M., Hoopes, T. G., Farb, A., Nott, S. H., Fischell, R. E., Fischell, D. R., Virmani, R., & Fischell, T. A. (1996). Inhibition of neointimal proliferation with low-dose irradiation from a β-particle-emitting stent. Circulation, 93(3), 529-536.