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 (N F) by reducing smooth muscle cell (SMC proliferation after balloon angiopla sty, but is complicated by subacute and late thrombosis. Rupture or abnorma lities of the internal elastic lamina (IEL) structure and subsequent exposu re of blood to the injured arterial wall can induce thrombosis and inflamma tion. The purpose of this study was to evaluate the effect of IR on the med ia and IEL after balloon overstretch injury in porcine coronary arteries. M ethods: Seventeen juvenile swine (25 coronary arteries) were injured by ove rstretch balloon and subsequently given IR at doses of 0 or 18 Gy Y-90 pres cribed to 1.2 mm from vessel wall inner surface. Two weeks following treatm ent, tissue sections were perfusion fixed and stained by hematoxylin-eosin or by Verhoeff-von Giesson. Smooth muscle cell alpha-actin was detected imm unocytochemically 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 ( RI) of the IEL was calculated rom the surface profile length and the straig ht-line length. Results: NF was markedly smaller after IR as compared to co ntrol treatment. Mural thrombi were increased significantly in irradiated v ersus 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 v s 74 +/- 10; P < 0. 001) despite a lack of difference in medial area. The s urface of the IEL was more irregular in irradiated arteries, particularly a t the medial breaks (RI = 20.1 +/- 3.1 vs 8.7 +/- 1.2; P < 0.001). When mur al thrombi were present, thrombus area correlated with RI (alpha = 0. 76; P < 0.01). Furthermore, in the irradiated group RI correlated positively wit h SMC density (alpha = 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 redu cing thrombosis and enhancing arterial healing.