Effects of brachytherapy on intimal hyperplasia in arteriovenous fistulas in a porcine model.
OBJECTIVE
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Rodriguez
Victor M
VM
Department of Surgery, University of California Davis Medical Center, Sacramento, CA 95817, USA.
Grove
Jay
J
Yelich
Susan
S
Pearson
David
D
Stein
Moni
M
Pevec
William C
WC
D000818:Animals; D001166:Arteriovenous Shunt, Surgical; D001918:Brachytherapy; D002339:Carotid Arteries / Q000473:pathology / Q000528:radiation effects; D016228:Endothelial Growth Factors / Q000528:radiation effects; D006965:Hyperplasia / Q000378:metabolism / Q000532:radiotherapy*; D007601:Jugular Veins / Q000473:pathology / Q000528:radiation effects; D023421:Models, Animal; D010982:Platelet-Derived Growth Factor / Q000528:radiation effects; D018709:Statistics, Nonparametric; D013552:Swine; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000528:radiation effects; D017539:Tunica Intima / Q000378:metabolism / Q000528:radiation effects*
D016228:Endothelial Growth Factors; D010982:Platelet-Derived Growth Factor; D014409:Tumor Necrosis Factor-alpha; C075278:platelet-derived growth factor A