Effects of Brachytherapy on Intimal Hyperplasia in Arteriovenous Fistulas in a Porcine Model

Abstract

The hypotheses of this investigation were that endovascular radiation would reduce intimal hyperplasia in arteriovenous fistulas (AVFs) and that this reduction would be associated with decreased expression of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF)-A, and tumor necrosis factor (TNF)-alpha. Bilateral end jugular vein-to-side carotid artery fistulas were constructed in pigs. At 48 hours, one AVF was randomly selected for endovascular radiation with (192) Iridium. The contralateral fistula received no radiation and served as a control. Animals in group 1 (n = 7) received 14 Gy of radiation at a depth of 2 mm and tissue was harvested at 29 days; animals in group 2 received 7 Gy of radiation at a depth of 2 mm and tissue was harvested at 29 days (n = 8); and animals in group 3 received 7 Gy of radiation at a depth of 2 mm and tissue was harvested at 56 days (n = 8). The area and maximum thickness of intimal hyperplasia were then measured blindly. Immunohistochemical results for VEGF, PDGF-A, and TNFalpha were obtained and analyzed blindly by assigning a score of 0-3, with 0 indicating no staining and 3 indicating maximum staining. Irradiation with 14 Gy caused severe fibrosis in the media of the vein, with thrombosis of three of seven AVFs. Compared with the control group, the group that underwent irradiation with 7 Gy had significantly reduced intimal area at 56 days (9.9 mm(2) +/- 4.9 vs 2.1 mm(2) +/- 1.1; P =.001). This reduction correlated with significant reduction in the expression of VEGF (score of 2.2 +/- 0.1 vs 1.2 +/- 0.2; P =.001) and TNFalpha (1.3 +/- 0.1 vs 0.9 +/- 0.1; P =.04). Fourteen grays is an excessive radiation dose for veins, causing medial fibrosis and thrombosis of the AVF. Irradiation with 7 Gy effectively inhibited the formation of intimal hyperplasia in AVF. This inhibition correlated with decreased expression of VEGF and TNFalpha.