Reduction of vein graft intimal hyperplasia by ex vivo treatment with desferrioxamine manganese.
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 mM) 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 microns (p < 0.05), in the middle segments 42.0 +/- 5.0 vs. 84.3 +/- 5.4 microns (p < 0.05) and in the distal segments 55.7 +/- 5.0 vs. 88.3 +/- 6.2 microns (p < 0.05) for treated and untreated animals, respectively. No evidence of long-term toxicity was found.(ABSTRACT TRUNCATED AT 250 WORDS)
Hagen
P O
PO
Department of Surgery, Duke University Medical Center, Durham, N.C. 27710.
Davies
M G
MG
Schuman
R W
RW
Murray
J J
JJ
D000818:Animals; D003676:Deferoxamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016166:Free Radical Scavengers; D005609:Free Radicals; D006965:Hyperplasia / Q000209:etiology / Q000517:prevention & control; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009942:Organometallic Compounds / Q000494:pharmacology; D011817:Rabbits; D014182:Transplantation, Autologous; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology; D014680:Veins / Q000637:transplantation*
D016166:Free Radical Scavengers; D005609:Free Radicals; D009942:Organometallic Compounds; C068338:manganese desferioxamine; D003676:Deferoxamine