Suppressors of oxygen metabolites fail to reduce vein graft intimal hyperplasia.
OBJECTIVE
To evaluate the role of reactive oxygen metabolites in the initiation of intimal hyperplasia of vein grafts inserted into the arterial circulation.


METHODS
University pathologic research laboratory.


METHODS
Sprague-Dawley rats.


METHODS
Animals were randomized to receive either the xanthine oxidase inhibitor allopurinol, the iron chelating agent starch-conjugated deferoxamine, or the free-radical scavenger 21-aminosteroid U74389G. Control animals were included for each group. The epigastric vein was inserted into the right common femoral artery. Vein grafts were harvested 30 days postoperatively. The degree of intimal hyperplasia at the two anastomoses as well as at the midgraft was calculated.


METHODS
The vein grafts were divided into three sections designated proximal anastomosis, midgraft, and distal anastomosis. Intimal and medial areas were determined in an observer-blind fashion and expressed as intimal area-medial area ratios.


RESULTS
Pretreatment of the animals with any of these agents resulted in no significant reduction in the degree of intimal hyperplasia in any treated groups compared with the control animals 30 days postoperatively.


CONCLUSIONS
Arterial reconstruction often involves interposition of vein segments into the arterial circulation. These veins are subject to ischemia and reperfusion, with the potential for generation of reactive oxygen metabolites and subsequent vein graft injury, resulting in intimal hyperplasia. We hypothesized that perioperative pharmacologic intervention either to scavenge or to reduce the production of reactive oxygen metabolites would attenuate the initial vein graft injury and thus limit the subsequent development of intimal hyperplasia. These data create doubt as to the influence of reactive oxygen metabolites in the initiation of intimal hyperplasia in the vein graft.
Gates
J D
JD
Department of Surgery, Harvard Medical School, Brigham and Women's Hospital, Boston, USA.
Hirsch
G M
GM
Karnovsky
M J
MJ
D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003676:Deferoxamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006965:Hyperplasia; D008297:Male; D011281:Pregnatrienes / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology*; D014680:Veins / Q000637:transplantation*
D000975:Antioxidants; D011281:Pregnatrienes; D017382:Reactive Oxygen Species; C074965:U 74389F; D000493:Allopurinol; D003676:Deferoxamine