Desferroxamine infusion increases cerebral blood flow: A potential association with hypoxia-inducible factor-1

Farzaneh A. Sorond, Michele L. Shaffer, Andrew L. Kung, Lewis A. Lipsitz

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Finding an effective means to improve cerebral perfusion during hypoxic/ischaemic stress is essential for neuroprotection. Studies in animal models of stroke have shown that desferroxamine activates HIF-1 (hypoxia-inducible factor-1), reduces brain damage and promotes functional recovery. The present study was designed to investigate the effects of desferroxamine infusion on the cerebral circulation in humans. Fifteen volunteers were enrolled in a randomized double-blind placebo-controlled crossover study. We measured cerebral blood flow velocity by transcranial Doppler ultrasonography in the middle cerebral artery, arterial blood pressure, end-tidal CO2, as well as HIF-1 protein and serum lactate dehydrogenase concentrations in response to 8 h of desferroxamine compared with placebo infusion. Cerebrovascular resistance was calculated from the ratio of steady-state beat-to-beat values for blood pressure to blood flow velocity. We found that desferroxamine infusion was associated with a significant cerebral vasodilation. Moreover, decreased cerebrovascular resistance was temporally correlated with an increased HIF-1 protein concentration as well as HIF-1 transcriptional activation, as measured by serum lactate dehydrogenase concentration. The findings of the present study provide preliminary data suggesting that activators of HIF-1, such as desferroxamine, may protect neurons against ischaemic injury by dilating cerebral vessels and enhancing cerebral perfusion.

Original languageEnglish (US)
Pages (from-to)771-779
Number of pages9
JournalClinical science
Volume116
Issue number10
DOIs
StatePublished - May 2009

Keywords

  • Cerebral blood flow
  • Desferroxamine
  • Hypoxia-inducible factor-1 (HIF-1)
  • Transcranial Doppler ultrasound

ASJC Scopus subject areas

  • Medicine(all)

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