Reduction of Vein Graft Intimal Hyperplasia by ex vivo Treatment with Desferrioxamine Manganese

Abstract

Reversed vein grafting exposes the venous tissue to a period of ischemia, reperfusion and subsequent free radical generation which may contribute to endothelial injury and/or damage, smooth muscle cell proliferation and the later development of intimal hyperplasia. The effects of ex vivo treatment with desferrioxamine Mn⁺³ (DFMn), a cell-permeable free radical scavenger, on the development of intimal hyperplasia in experimental vein grafts was examined. Twenty New Zealand white rabbits received a reversed vein interposition bypass graft into the ipsilateral common carotid artery. Ten explanted veins were immersed in a heparinized (5 IU/ml) saline solution, and 10 others were immersed in a similar solution containing DFMn (1 m M) for 45 min prior to reimplantation. There were no short-term functional or morphologic toxic side effects associated with DFMn treatment on either the endothelial or smooth muscle cells of the veins. At 28 days, grafts (n = 20) were perfusion-fixed in vivo for histological and morphometric studies. There was a significant reduction in intimal thickening in the DFMn-treated group compared to the untreated group. The thicknesses of the intimal hyperplasia in the proximal segments were 50.6 ± 6.3 vs. 76.9 ± 3.2 µm (p& < 0.05), in the middle segments 42.0 ± 5.0 vs. 84.3 ± 5.4 µm (p < 0.05) and in the distal segments 55.7 ± 5.0 vs. 88.3 ± 6.2 µm (p& < 0.05) for treated and untreated animals, respectively. No evidence of long-term toxicity was found. These results indicate that a single ex vivo treatment with DFMn reduces graft intimal hyperplasia normally present at 4 weeks and suggests that oxygen free radicals may play a role in the initiation of vein graft intimal hyperplasia.