@article{af11e7c685ff48f2b6ef44159f6a43a0,
title = "High dose rate intracoronary radiation for inhibition of neointimal formation in the stented and balloon-injured porcine models of restenosis: Angiographic, morphometric, and histopathologic analyses",
abstract = "Purpose: We examined the effects of intracoronary irradiation delivered at a high dose rate on neointimal hyperplasia after injury induced by two methods: balloon overstretch injury, and stent implantation in a porcine model of coronary restenosis. Methods and Materials: In 34 Hanford miniature swine, a segment of each coronary artery was targeted for injury and treatment. The artery segments were treated with 192Ir at doses of 10 Gy over 4 min (eight animals), 15 Gy over 6 min (nine animals), 25 Gy over 10 min (nine animals) or control (simulation wire only; eight animals). The treated segments were subjected to stent implantation (left anterior descending and right coronary artery) or balloon overstretch (circumflex) injury. Twenty-eight days later, repeat coronary angiography and sacrifice were done. Quantitative coronary angiography, morphometry, and extensive histopathologic analyses were carried out in a blinded fashion. Results: The change in minimal lumen diameter from postinjury to presacrifice in the stent-injured left anterior descending was -0.79 ± 0.34 (mean: ± SD) mm in the control group, compared to -0.43 ± 0.35 mm in the 15 Gy (p = 0.04) and - 0.21 ± 0.50 mm in the 25 Gy (p = 0.01) groups; and in the balloon-injured circumflex was -0.31 ± 0.22 mm in the control group compared to -0.03 ± 0.18 mm in the 10 Gy (p = 0.05) and 0.00 ± 0.33 in the 15 Gy (p = 0.01) groups. Percent area stenosis in the left anterior descending was 36 ± 9% in the control group compared to 18 ± 12% in the 15 Gy (p = 0.003) and 11 ± 11% in the 25 Gy (p < 0.001) groups; and in the circumflex was 16 ± 10% in the control groups, compared to 5 ± 5% in the 15 Gy (p = 0.02) and 2 ± 2% in the 25 Gy (p = 0.009) groups. Histopathology showed a striking reduction in the amount of neointima in the irradiated arteries compared with control vessels. Other radiation effects were stromal fibrin exudate, thinning of the media, and adventitial fibrosis and leukocyte infiltration in the radiated arterial segments. Conclusions: High dose rate intracoronary irradiation with 192Ir effectively inhibits intimal proliferation after stent-induced as well as balloon-overstretch injury. This shorter treatment time (4 to 10 min) may provide a clinically practical approach to the prevention of restenosis after angioplasty.",
keywords = "Angioplasty, Radiation, Restenosis",
author = "Wojciech Mazur and Ali, {M. Nadir} and Khan, {M. Musa} and Dabaghi, {Salim F.} and DeFelice, {Clement A.} and Pierre Paradis and Butler, {E. Brian} and Wright, {Ann E.} and Fajardo, {Luis F.} and French, {Brent A.} and Raizner, {Albert E.}",
note = "Funding Information: Acknowledgeme?&--This work was supported by Cardiac Catheterization Laboratories Research Fund of The Methodist Hospita1 Foundation and by NeoCardia, Inc. Houston. TX. We thank *Department of Medicine. Section of Cardiology, {\textquoteleft}Department of Radiation Oncology, Baylor College of Medicine and The Methodist Hospital, {\textquoteleft}Consulting Medical Physicist, Houston, TX; “Department of Pathology . Veterans Affairs Medical Center, Stanford University School of Medicine, Palo Alto. CA Purpose: We examined the effects of intracoronary irradiation delivered at a high dose rate on neointimal hy-ma after injury induced by two methods: balloon overstretch injury, and stent implantation in a porcine mode1 of coronary restenosis. Methods and Materials: In 34 Hanford miniature swine, a segment of each coronary artery was tapted for iqjnry and treatment. The artery segments were treated with 19*Ir at doses of 10 Gy over 4 min (eight animals), 15 Gy over 6 mln (nine animals), 25 Gy over 10 min (nine animals) or control (simulation wire only; eight &mals). The treated segments were subjected to stent implantation (left anterior descending and right coronary artery) or balloon overstretch (circumflex) injury. Twenty-eight days later, repeat coronary angiogr8phy and sacrifice were done. Quantitative coronary angiography, morphometry, and extensive bistopathologic analyses were carried out in a blinded fashion. Results: The change in minimal lumen diameter from postinjury to presacrifice in the stent+jured I& anterior descending was -0.79 +-0.34 (mean: ? SD) mm in the control group, compared to -0.43 t 0.35 mm in the 15 Gy (p = 0.04) and -0.21 2 0.50 mm in the 25 Gy @ = 0.01) groups; and in the balloon-inJured circumflex was -0.31 t 0.22 mm in the control group compared to -0.03 ? 0.18 mm in the 10 Gy (p = 0.05) and 0.00 C 0.33 in the 15 Gy @ = 0.01) groups. Percent area stenosis in the left anterior descending was 36 t 9% in the control group compared to 18 t 12% in the 15 Gy (p = 0.003) and 11 t 11% in the 25 Gy (p < 0.001) groups; and in the circumflex was 16 2 10% in the control groups, compared to 5 2 5% in the 15 Gy (p = 0.02) and 2 + 2% in the 25 Gy @ = 0.009) groups. Histopathology showed a striking reduction in the amount of neoiatima in the irradiated arteries compared with control vessels. Other radiation effects were stromai fibrin exudate, thinning of the media, and adventitial fibrosis and leukocyte infiltration in the radiated arterial segments. Conctuskms: High dose rate intracoronary irradiation with 19*Ir effectively inhibits inthnal proliferation 8fter stent-induced as well as balloon-overstretch injury. This shorter treatment time (4 to 10 tin) may provide a clhdcatly practical approach to the prevention of restenosis after angioplasty. Copyright 0 1996 Elsevier Science Inc.",
year = "1996",
month = nov,
day = "1",
doi = "10.1016/S0360-3016(96)00298-2",
language = "English (US)",
volume = "36",
pages = "777--788",
journal = "International Journal of Radiation Oncology Biology Physics",
issn = "0360-3016",
publisher = "Elsevier",
number = "4",
}