Inhibition of delayed arterial narrowing by the iron-chelating agent deferoxamine

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  • 1 Department of Neurological Surgery, University of Washington and Veterans Administration Medical Center, Seattle, Washington
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✓ 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.

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Contributor Notes

Address reprint requests to: Marc R. Mayberg, M.D., Department of Neurological Surgery, RI-20, University of Washington, Seattle, Washington 98195.
  • 1.

    Angel MF, , Haddad J Jr, & Abramson M: A free radical scavenger reduces hematoma-induced flap necrosis in Fischer rats. Otolaryngol Head Neck Surg 96:9698, 1987 Angel MF, Haddad J Jr, Abramson M: A free radical scavenger reduces hematoma-induced flap necrosis in Fischer rats. Otolaryngol Head Neck Surg 96:96–98, 1987

    • Search Google Scholar
    • Export Citation
  • 2.

    Aust SD, & White BC: Iron chelation prevents tissue injury following ischemia. Adv Free Rad Biol Med 1:117, 1985 Aust SD, White BC: Iron chelation prevents tissue injury following ischemia. Adv Free Rad Biol Med 1:1–17, 1985

    • Search Google Scholar
    • Export Citation
  • 3.

    Brandt L, , Ljunggren B, & Andersson KE, et al. : Vasoconstrictive effects of human post-hemorrhagic cerebrospinal fluid on cat pial arterioles in situ. J Neurosurg 54:351356, 1981 Brandt L, Ljunggren B, Andersson KE, et al: Vasoconstrictive effects of human post-hemorrhagic cerebrospinal fluid on cat pial arterioles in situ. J Neurosurg 54:351–356, 1981

    • Search Google Scholar
    • Export Citation
  • 4.

    Braughler JM, , Chase RL, & Pregenzer JF: Stimulation and inhibition of iron-dependent lipid peroxidation by desferrioxamine. Biochem Biophys Res Commun 153:933938, 1988 Braughler JM, Chase RL, Pregenzer JF: Stimulation and inhibition of iron-dependent lipid peroxidation by desferrioxamine. Biochem Biophys Res Commun 153:933–938, 1988

    • Search Google Scholar
    • Export Citation
  • 5.

    Carrell RW, , Winterbourn CC, & Rachmilewitz EA: Annotation: activated oxygen and haemolysis. Br J Haematol 30:259264, 1975 Carrell RW, Winterbourn CC, Rachmilewitz EA: Annotation: activated oxygen and haemolysis. Br J Haematol 30:259–264, 1975

    • Search Google Scholar
    • Export Citation
  • 6.

    Duff TA, , Feilbach JA, & Yusuf Q, et al. : Bilirubin and the induction of intracranial arterial spasm. J Neurosurg 69:593598, 1988 Duff TA, Feilbach JA, Yusuf Q, et al: Bilirubin and the induction of intracranial arterial spasm. J Neurosurg 69:593–598, 1988

    • Search Google Scholar
    • Export Citation
  • 7.

    Duff TA, , Louie J, & Feilbach JA, et al. : Erythrocytes are essential for development of cerebral vasculopathy resulting from subarachnoid hemorrhage in cats. Stroke 19:6872, 1988 Duff TA, Louie J, Feilbach JA, et al: Erythrocytes are essential for development of cerebral vasculopathy resulting from subarachnoid hemorrhage in cats. Stroke 19:68–72, 1988

    • Search Google Scholar
    • Export Citation
  • 8.

    Fox JL: Intracranial vasospasm: a study with iron compounds. Surg Neurol 11:363368, 1979 Fox JL: Intracranial vasospasm: a study with iron compounds. Surg Neurol 11:363–368, 1979

    • Search Google Scholar
    • Export Citation
  • 9.

    Fujii S, & Fujitsu K: Experimental vasospasm in cultured arterial smooth-muscle cells. Part 1: Contractile and ultrastructural changes caused by oxyhemoglobin. J Neurosurg 69:9297, 1988 Fujii S, Fujitsu K: Experimental vasospasm in cultured arterial smooth-muscle cells. Part 1: Contractile and ultrastructural changes caused by oxyhemoglobin. J Neurosurg 69:92–97, 1988

    • Search Google Scholar
    • Export Citation
  • 10.

    Fujiwara S, , Kassell NF, & Sasaki T, et al. : Selective hemoglobin inhibition of endothelium-dependent vasodilation of rabbit basilar artery. J Neurosurg 64:445452, 1986 Fujiwara S, Kassell NF, Sasaki T, et al: Selective hemoglobin inhibition of endothelium-dependent vasodilation of rabbit basilar artery. J Neurosurg 64:445–452, 1986

    • Search Google Scholar
    • Export Citation
  • 11.

    Graf E, , Mahoney JR, & Bryant RG, et al. : Iron-catalyzed hydroxyl radical formation. Stringent requirement for free iron coordination site. J Biol Chem 259:36203624, 1984 Graf E, Mahoney JR, Bryant RG, et al: Iron-catalyzed hydroxyl radical formation. Stringent requirement for free iron coordination site. J Biol Chem 259:3620–3624, 1984

    • Search Google Scholar
    • Export Citation
  • 12.

    Gutteridge JM, , Richmond R, & Halliwell B: Inhibition of the iron-catalysed formation of hydroxyl radicals from superoxide and of lipid peroxidation by desferrioxamine. Biochem J 184:469472, 1979 Gutteridge JM, Richmond R, Halliwell B: Inhibition of the iron-catalysed formation of hydroxyl radicals from superoxide and of lipid peroxidation by desferrioxamine. Biochem J 184:469–472, 1979

    • Search Google Scholar
    • Export Citation
  • 13.

    Harada T, , Suzuki Y, & Satoh S, et al. : Blood component induction of cerebral vasospasm. Neurosurgery 27:252256, 1990 Harada T, Suzuki Y, Satoh S, et al: Blood component induction of cerebral vasospasm. Neurosurgery 27:252–256, 1990

    • Search Google Scholar
    • Export Citation
  • 14.

    Ikeda Y, , Ikeda K, & Long DM: Comparative study of different iron-chelating agents in cold-induced brain edema. Neurosurgery 24:820824, 1989 Ikeda Y, Ikeda K, Long DM: Comparative study of different iron-chelating agents in cold-induced brain edema. Neurosurgery 24:820–824, 1989

    • Search Google Scholar
    • Export Citation
  • 15.

    Keberle H: The biochemistry of desferrioxamine and its relation to iron metabolism. Ann NY Acad Sci 119:758768, 1964 Keberle H: The biochemistry of desferrioxamine and its relation to iron metabolism. Ann NY Acad Sci 119:758–768, 1964

    • Search Google Scholar
    • Export Citation
  • 16.

    Macdonald RL, & Weir BKA: A review of hemoglobin and the pathogenesis of cerebral vasospasm. Stroke 22:971982, 1991 Macdonald RL, Weir BKA: A review of hemoglobin and the pathogenesis of cerebral vasospasm. Stroke 22:971–982, 1991

    • Search Google Scholar
    • Export Citation
  • 17.

    Mayberg MR, , Okada T, & Bark DH: The role of hemoglobin in arterial narrowing after subarachnoid hemorrhage. J Neurosurg 72:634640, 1990 Mayberg MR, Okada T, Bark DH: The role of hemoglobin in arterial narrowing after subarachnoid hemorrhage. J Neurosurg 72:634–640, 1990

    • Search Google Scholar
    • Export Citation
  • 18.

    Mayberg MR, , Okada T, & Bark DH: The significance of morphological change in cerebral arteries after subarachnoid hemorrhage. J Neurosurg 72:626633, 1990 Mayberg MR, Okada T, Bark DH: The significance of morphological change in cerebral arteries after subarachnoid hemorrhage. J Neurosurg 72:626–633, 1990

    • Search Google Scholar
    • Export Citation
  • 19.

    McIlhany MP, , Johns LM, & Leipzig T, et al. : In vivo characterization of vasocontractile activities in erythrocytes. J Neurosurg 58:356361, 1983 McIlhany MP, Johns LM, Leipzig T, et al: In vivo characterization of vasocontractile activities in erythrocytes. J Neurosurg 58:356–361, 1983

    • Search Google Scholar
    • Export Citation
  • 20.

    Misra HP, & Fridovich I: The generation of superoxide radical during the autoxidation of hemoglobin. J Biol Chem 247:69606962, 1972 Misra HP, Fridovich I: The generation of superoxide radical during the autoxidation of hemoglobin. J Biol Chem 247:6960–6962, 1972

    • Search Google Scholar
    • Export Citation
  • 21.

    Okada T, , Harada T, & Bark DH, et al. : A rat femoral artery model for vasospasm. Neurosurgery 27:349356, 1990 Okada T, Harada T, Bark DH, et al: A rat femoral artery model for vasospasm. Neurosurgery 27:349–356, 1990

    • Search Google Scholar
    • Export Citation
  • 22.

    Osaka K: Prolonged vasospasm produced by the breakdown products of erythrocytes. J Neurosurg 47:403411, 1977 Osaka K: Prolonged vasospasm produced by the breakdown products of erythrocytes. J Neurosurg 47:403–411, 1977

    • Search Google Scholar
    • Export Citation
  • 23.

    Ozaki N, & Mullan S: Possible role of the erythrocytes in causing prolonged cerebral vasospasm. J Neurosurg 51:773778, 1979 Ozaki N, Mullan S: Possible role of the erythrocytes in causing prolonged cerebral vasospasm. J Neurosurg 51:773–778, 1979

    • Search Google Scholar
    • Export Citation
  • 24.

    Sano K, , Asano T, & Tanishima T, et al. : Lipid peroxidation as a cause of cerebral vasospasm. Neurol Res 2:253272, 1980 Sano K, Asano T, Tanishima T, et al: Lipid peroxidation as a cause of cerebral vasospasm. Neurol Res 2:253–272, 1980

    • Search Google Scholar
    • Export Citation
  • 25.

    Sinaceur J, , Ribière C, & Nordmann J, et al. : Desferrioxamine: a scavenger of superoxide radicals? Biochem Pharmacol 33:16931694, 1984 Sinaceur J, Ribière C, Nordmann J, et al: Desferrioxamine: a scavenger of superoxide radicals? Biochem Pharmacol 33:1693–1694, 1984

    • Search Google Scholar
    • Export Citation
  • 26.

    Vollmer DG, , Hongo K, & Ogawa H, et al. : A study of the effectiveness of the iron-chelating agent deferoxamine as vasospasm prophylaxis in a rabbit model of subarachnoid hemorrhage. Neurosurgery 28:2732, 1991 Vollmer DG, Hongo K, Ogawa H, et al: A study of the effectiveness of the iron-chelating agent deferoxamine as vasospasm prophylaxis in a rabbit model of subarachnoid hemorrhage. Neurosurgery 28:27–32, 1991

    • Search Google Scholar
    • Export Citation

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