Inhibition of delayed arterial narrowing by the iron-chelating agent deferoxamine.
The potential role of iron in cerebral vasospasm was examined in the rat femoral artery model by the perivascular application of deferoxamine, a ferric ion chelator and antioxidant. In 25 rats, platelet-rich plasma or fresh autologous whole blood containing deferoxamine at concentrations of 1, 5, 10, or 15 mg/ml was applied to the adventitial surface of the femoral artery in a Silastic cuff to insure chronic exposure to the vessel wall. At 7 days, contralateral femoral arteries exposed to whole blood showed a 70% reduction in luminal cross-sectional area and morphological changes associated with vasospasm. Application of platelet-rich plasma or whole blood containing deferoxamine at 25 mg/ml produced no significant arterial narrowing or structural changes; significant intermediate reductions in arterial narrowing were observed at deferoxamine concentrations of 5 and 10 mg/ml. Presaturation deferoxamine (10 mg/ml) with excess ferric ion prior to application eliminated the protective effect. In addition, deferoxamine chelated the ferric ion released from incubated whole blood in vitro over 7 days in a dose-dependent manner consistent with its protective effect in vivo. Ferric ion may influence the development of chronic arterial narrowing after subarachnoid hemorrhage by a variety of mechanisms.
Harada
T
T
Department of Neurological Surgery, University of Washington, Seattle.
Mayberg
M R
MR
D000818:Animals; D003676:Deferoxamine / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism; D066298:In Vitro Techniques; D007501:Iron / Q000502:physiology*; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control*; D015227:Lipid Peroxidation; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000503:physiopathology
D005609:Free Radicals; D007501:Iron; D003676:Deferoxamine