Effects of endovascular radiation from a β-particle-emitting stent in a porcine coronary restenosis model: A dose-response study

Andrew J. Carter, John R. Laird, Lynn R. Bailey, Timothy G. Hoopes, Andrew Farb, David R. Fischell, Robert E. Fischell, Tim A. Fischell, Renu Virmani

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

Background: Neointimal formation causes restenosis after intracoronary stent placement. Endovascular radiation delivered via a stent has been shown to reduce neointimal formation after placement in porcine and rabbit iliac arteries. THe objective of this study was to evaluate the dose-related effects of a β-particle-emitting radioactive stent in a porcine coronary restenosis model. Methods and Results: Thirty-seven swine underwent placement of 35 nonradioactive and 39 β-particle-emitting stents with activity levels of 23.0, 14.0, 6.0, 3.0, 1.0, 0.5, and 0.15 μCi of 32P. Treatment effect was assessed by histological analysis 28 days after stent placement. Neointimal and medial smooth muscle cell density were inversely related to increasing stent activity. The neointima of the high-activity (3.0- to 23.0- μCi) stents consisted of fibrin, erythrocytes, occasional inflammatory cells, and smooth muscle cells with partial endothelialization of the luminal surface. In the 1.0-μCi stents, the neointima was expanded and consisted of smooth muscle cells and a proteoglycan-rich matrix. The neointima of the low- activity (0.15- and 0.5-μCi) stents was composed of smooth muscle cells and matrix with complete endothelialization of the luminal surface. At low and high stent activities, there was a reduction in neointimal area (low, 1.63±0.67 mm 2 and high, 1.73±0.97 mm 2 versus control, 2.40±0.87 mm 2) and percent area stenosis (low, 26±7% and high, 26±12%) compared with control stents (37±12%, P≤.01). The 1.0-μCi stents, however, had greater neointimal formation (4.67±1.50 mm 2) and more luminal narrowing (64±16%) than the control stents (P<.0001). Conclusions: The differential response to the doses of continuous β-particle irradiation used in this experimental model suggests a complex biological interaction of endovascular radiation and vascular repair after stent placement. Further study is required to determine the clinical potential for this therapy to prevent stent restenosis.

Original languageEnglish (US)
Pages (from-to)2364-2368
Number of pages5
JournalCirculation
Volume94
Issue number10
StatePublished - 1996
Externally publishedYes

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Coronary Restenosis
Radiation Effects
Stents
Swine
Neointima
Smooth Muscle Myocytes
Radiation
Iliac Artery

Keywords

  • arteries
  • stenosis
  • stents

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Carter, A. J., Laird, J. R., Bailey, L. R., Hoopes, T. G., Farb, A., Fischell, D. R., ... Virmani, R. (1996). Effects of endovascular radiation from a β-particle-emitting stent in a porcine coronary restenosis model: A dose-response study. Circulation, 94(10), 2364-2368.

Effects of endovascular radiation from a β-particle-emitting stent in a porcine coronary restenosis model : A dose-response study. / Carter, Andrew J.; Laird, John R.; Bailey, Lynn R.; Hoopes, Timothy G.; Farb, Andrew; Fischell, David R.; Fischell, Robert E.; Fischell, Tim A.; Virmani, Renu.

In: Circulation, Vol. 94, No. 10, 1996, p. 2364-2368.

Research output: Contribution to journalArticle

Carter, AJ, Laird, JR, Bailey, LR, Hoopes, TG, Farb, A, Fischell, DR, Fischell, RE, Fischell, TA & Virmani, R 1996, 'Effects of endovascular radiation from a β-particle-emitting stent in a porcine coronary restenosis model: A dose-response study', Circulation, vol. 94, no. 10, pp. 2364-2368.
Carter AJ, Laird JR, Bailey LR, Hoopes TG, Farb A, Fischell DR et al. Effects of endovascular radiation from a β-particle-emitting stent in a porcine coronary restenosis model: A dose-response study. Circulation. 1996;94(10):2364-2368.
Carter, Andrew J. ; Laird, John R. ; Bailey, Lynn R. ; Hoopes, Timothy G. ; Farb, Andrew ; Fischell, David R. ; Fischell, Robert E. ; Fischell, Tim A. ; Virmani, Renu. / Effects of endovascular radiation from a β-particle-emitting stent in a porcine coronary restenosis model : A dose-response study. In: Circulation. 1996 ; Vol. 94, No. 10. pp. 2364-2368.
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abstract = "Background: Neointimal formation causes restenosis after intracoronary stent placement. Endovascular radiation delivered via a stent has been shown to reduce neointimal formation after placement in porcine and rabbit iliac arteries. THe objective of this study was to evaluate the dose-related effects of a β-particle-emitting radioactive stent in a porcine coronary restenosis model. Methods and Results: Thirty-seven swine underwent placement of 35 nonradioactive and 39 β-particle-emitting stents with activity levels of 23.0, 14.0, 6.0, 3.0, 1.0, 0.5, and 0.15 μCi of 32P. Treatment effect was assessed by histological analysis 28 days after stent placement. Neointimal and medial smooth muscle cell density were inversely related to increasing stent activity. The neointima of the high-activity (3.0- to 23.0- μCi) stents consisted of fibrin, erythrocytes, occasional inflammatory cells, and smooth muscle cells with partial endothelialization of the luminal surface. In the 1.0-μCi stents, the neointima was expanded and consisted of smooth muscle cells and a proteoglycan-rich matrix. The neointima of the low- activity (0.15- and 0.5-μCi) stents was composed of smooth muscle cells and matrix with complete endothelialization of the luminal surface. At low and high stent activities, there was a reduction in neointimal area (low, 1.63±0.67 mm 2 and high, 1.73±0.97 mm 2 versus control, 2.40±0.87 mm 2) and percent area stenosis (low, 26±7{\%} and high, 26±12{\%}) compared with control stents (37±12{\%}, P≤.01). The 1.0-μCi stents, however, had greater neointimal formation (4.67±1.50 mm 2) and more luminal narrowing (64±16{\%}) than the control stents (P<.0001). Conclusions: The differential response to the doses of continuous β-particle irradiation used in this experimental model suggests a complex biological interaction of endovascular radiation and vascular repair after stent placement. Further study is required to determine the clinical potential for this therapy to prevent stent restenosis.",
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T1 - Effects of endovascular radiation from a β-particle-emitting stent in a porcine coronary restenosis model

T2 - A dose-response study

AU - Carter, Andrew J.

AU - Laird, John R.

AU - Bailey, Lynn R.

AU - Hoopes, Timothy G.

AU - Farb, Andrew

AU - Fischell, David R.

AU - Fischell, Robert E.

AU - Fischell, Tim A.

AU - Virmani, Renu

PY - 1996

Y1 - 1996

N2 - Background: Neointimal formation causes restenosis after intracoronary stent placement. Endovascular radiation delivered via a stent has been shown to reduce neointimal formation after placement in porcine and rabbit iliac arteries. THe objective of this study was to evaluate the dose-related effects of a β-particle-emitting radioactive stent in a porcine coronary restenosis model. Methods and Results: Thirty-seven swine underwent placement of 35 nonradioactive and 39 β-particle-emitting stents with activity levels of 23.0, 14.0, 6.0, 3.0, 1.0, 0.5, and 0.15 μCi of 32P. Treatment effect was assessed by histological analysis 28 days after stent placement. Neointimal and medial smooth muscle cell density were inversely related to increasing stent activity. The neointima of the high-activity (3.0- to 23.0- μCi) stents consisted of fibrin, erythrocytes, occasional inflammatory cells, and smooth muscle cells with partial endothelialization of the luminal surface. In the 1.0-μCi stents, the neointima was expanded and consisted of smooth muscle cells and a proteoglycan-rich matrix. The neointima of the low- activity (0.15- and 0.5-μCi) stents was composed of smooth muscle cells and matrix with complete endothelialization of the luminal surface. At low and high stent activities, there was a reduction in neointimal area (low, 1.63±0.67 mm 2 and high, 1.73±0.97 mm 2 versus control, 2.40±0.87 mm 2) and percent area stenosis (low, 26±7% and high, 26±12%) compared with control stents (37±12%, P≤.01). The 1.0-μCi stents, however, had greater neointimal formation (4.67±1.50 mm 2) and more luminal narrowing (64±16%) than the control stents (P<.0001). Conclusions: The differential response to the doses of continuous β-particle irradiation used in this experimental model suggests a complex biological interaction of endovascular radiation and vascular repair after stent placement. Further study is required to determine the clinical potential for this therapy to prevent stent restenosis.

AB - Background: Neointimal formation causes restenosis after intracoronary stent placement. Endovascular radiation delivered via a stent has been shown to reduce neointimal formation after placement in porcine and rabbit iliac arteries. THe objective of this study was to evaluate the dose-related effects of a β-particle-emitting radioactive stent in a porcine coronary restenosis model. Methods and Results: Thirty-seven swine underwent placement of 35 nonradioactive and 39 β-particle-emitting stents with activity levels of 23.0, 14.0, 6.0, 3.0, 1.0, 0.5, and 0.15 μCi of 32P. Treatment effect was assessed by histological analysis 28 days after stent placement. Neointimal and medial smooth muscle cell density were inversely related to increasing stent activity. The neointima of the high-activity (3.0- to 23.0- μCi) stents consisted of fibrin, erythrocytes, occasional inflammatory cells, and smooth muscle cells with partial endothelialization of the luminal surface. In the 1.0-μCi stents, the neointima was expanded and consisted of smooth muscle cells and a proteoglycan-rich matrix. The neointima of the low- activity (0.15- and 0.5-μCi) stents was composed of smooth muscle cells and matrix with complete endothelialization of the luminal surface. At low and high stent activities, there was a reduction in neointimal area (low, 1.63±0.67 mm 2 and high, 1.73±0.97 mm 2 versus control, 2.40±0.87 mm 2) and percent area stenosis (low, 26±7% and high, 26±12%) compared with control stents (37±12%, P≤.01). The 1.0-μCi stents, however, had greater neointimal formation (4.67±1.50 mm 2) and more luminal narrowing (64±16%) than the control stents (P<.0001). Conclusions: The differential response to the doses of continuous β-particle irradiation used in this experimental model suggests a complex biological interaction of endovascular radiation and vascular repair after stent placement. Further study is required to determine the clinical potential for this therapy to prevent stent restenosis.

KW - arteries

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