Decreased adventitial neovascularization after intracoronary irradiation in swine: A time course study

Background: Intracoronary radiation (IR) suppresses the formation of neoint ima after arterial injury in swine, through mechanisms incompletely underst ood. Neointimal development appears related to expansion of adventitial mic rovessels; we therefore examined the hypothesis that IR inhibits neointima formation through an anti-angiogenic effect. Methods and Results: Juvenile swine were treated with either 0 or 15 Gy Ir- 192 (gamma -source) and euthanized 3, 7, or 14 days later or treated with 1 8 Gy Y-90 (beta -sonrce) acid euthanized after 14 days. Adventitial area (A A), intimal area (IA), IA corrected for medial fracture length, and adventi tial vessel area were assessed in both injured and uninjured segments by co mputer-aided histomorphometry on Verhoeff-Von Giesson stained sections. Adv entitial vessel count (AVC) was enumerated visually on hematoxylin and eosi n stained sections and confirmed by anti-factor VIII-associated antigen imm unostaining for endothelial cells, AA and IA were reduced in injured arteri es subjected to IR as compared to controls. The AVC was significantly lower in injured irradiated arterial segments as well as all uninjured segments as compared with injured control segments. In the injured acid irradiated a rteries, the AVC remained unchanged at 3, 7, and 14 days. The injured segme nts of arteries treated with IR demonstrated a significantly lower adventit ial microvessel density (AVC/AA) as compared to the injured control segment s. Comparison of gamma- and beta -irradiation at 14 days did not show any d ifferences for vessel parameters and measurements of adventitial microvesse ls, IA and AVC were correlated positively (R-2 = 0.63, alpha = 0.79, p < 0. 01). Conclusion: IR induced an early and sustained anti-angiogenic effect betwee n 3 and 14 days. The relation between IA and AVC may indicate an antiprolif erative effect associated with an anti-angiogenic effect independent of the type of radiation. CONDENSED ABSTRACT Intracoronary radiation suppresses neointima formation a fter arterial injury in swine, through mechanisms and with consequences tha t are not fully known. Reduction of angiogenesis may inhibit restenosis, In the present study, intimal area and adventitial area were reduced in the i ntracoronary radiation groups 3-14 days after arterial injury as compared t o their respective controls, with a parallel reduction in the adventitial v essel count and adventitial vessel density. Intimal area and adventitial ve ssel count were correlated positively. Neointima reduction after intracoron ary radiation may depend not only on an antiproliferative effect but also o n an anti-angiogenic effect. (C) 2001 Elsevier Science Inc.