Surface profile of the internal elastic lamina may modulate thrombosis following intracoronary radiation in balloon-injured porcine arteries

Background: Intracoronary radiation (IR) can prevent neointima formation (NF) by reducing smooth muscle cell (SMC) proliferation after balloon angioplasty, but is complicated by subacute and late thrombosis. Rupture or abnormalities of the internal elastic lamina (IEL) structure and subsequent exposure of blood to the injured arterial wall can induce thrombosis and inflammation. The purpose of this study was to evaluate the effect of IR on the media and IEL after balloon overstretch injury in porcine coronary arteries. Methods: Seventeen juvenile swine (25 coronary arteries) were injured by overstretch balloon and subsequently given IR at doses of 0 or 18 Gy⁹⁰Y prescribed to 1.2 mm from vessel wall inner surface. Two weeks following treatment, tissue sections were perfusion fixed and stained by hematoxylin-eosin or by Verhoeff-von Giesson. Smooth muscle cell α-actin was detected immunocytochemically and quantified by digital image analysis using arbitrary density units. Histomorphometry was carried out to assess intimal area (IA) and IA corrected for medial fracture length (IA/FL). The roughness index (R1) of the 1EL was calculated from the surface profile length and the straight-line length. Results: NF was markedly smaller after IR as compared to control treatment. Mural thrombi were increased significantly in irradiated versus control arteries (11/14 [78%] vs 1/11 [9%]; P < 0.001). A significant decrease in SMC density was observed in the irradiated group (128 ± 13 vs 74 ± 10; P < 0.001) despite a lack of difference in medial area. The surface of the IEL was more irregular in irradiated arteries, particularly at the medial breaks (RI = 20.1 ± 3.1 vs 8.7 ± 1.2; P < 0.001). When mural thrombi were present, thrombus area correlated with RI (α = 0.76; P < 0.01). Furthermore, in the irradiated group RI correlated positively with SMC density (α = 0.64; P < 0.01). Conclusion: Medial structure and RI may be useful parameters by which to assess arterial healing following IR. These findings may influence the design of future IR studies aimed at reducing thrombosis and enhancing arterial healing.