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

Purpose: We examined the effects of intracoronary irradiation delivere d at a high dose rate on neointimal hyperplasia after injury induced b y two methods: balloon overstretch injury, and stent implantation in a porcine model of coronary restenosis, Methods and Materials: In 34 Ha nford miniature swine, a segment of each coronary artery was targeted for injury and treatment, The artery segments were treated with Ir-192 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 im plantation (left anterior descending and right coronary artery) or bal loon overstretch (circumflex) injury, Twenty-eight days later, repeat coronary angiography and sacrifice were done, Quantitative coronary an giography, morphometry, and extensive histopathologic analyses were ca rried out in a blinded fashion, Results: The change in minimal lumen d iameter from postinjury to presacrifice in the stent-injured left ante rior descending was -0.79 +/- 0.34 (mean: +/- SD) mm in the control gr oup, 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 -0.0 3 +/- 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 descendin g 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) grou ps, Histopathology showed a striking reduction in the amount of neoint ima in the irradiated arteries compared with control vessels, Other ra diation effects were stromal fibrin exudate, thinning of the media, an d adventitial fibrosis and leukocyte infiltration in the radiated arte rial segments. Conclusions: High dose rate intracoronary irradiation w ith Ir-192 effectively inhibits intimal proliferation after stent-indu ced as well as balloon-overstretch injury, This shorter treatment time (4 to 10 min) may provide a clinically practical approach to the prev ention of restenosis after angioplasty Copyright (C) 1996 Elsevier Sci ence Inc.