PMID- 19014354
OWN - NLM
STAT- MEDLINE
DCOM- 20090731
LR  - 20220304
IS  - 1470-8736 (Electronic)
IS  - 0143-5221 (Print)
IS  - 0143-5221 (Linking)
VI  - 116
IP  - 10
DP  - 2009 May
TI  - Desferroxamine infusion increases cerebral blood flow: a potential association 
      with hypoxia-inducible factor-1.
PG  - 771-9
LID - 10.1042/CS20080320 [doi]
AB  - 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 CO(2), 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.
FAU - Sorond, Farzaneh A
AU  - Sorond FA
AD  - Department of Neurology, Stroke Division, Brigham and Women's Hospital, Boston, 
      MA 02115, USA. fsorond@partners.org
FAU - Shaffer, Michele L
AU  - Shaffer ML
FAU - Kung, Andrew L
AU  - Kung AL
FAU - Lipsitz, Lewis A
AU  - Lipsitz LA
LA  - eng
GR  - Z01 AG000294/ImNIH/Intramural NIH HHS/United States
GR  - AG08812/AG/NIA NIH HHS/United States
GR  - K12AG00294/AG/NIA NIH HHS/United States
GR  - P60 AG008812/AG/NIA NIH HHS/United States
GR  - T32 AG023480/AG/NIA NIH HHS/United States
GR  - AG05134/AG/NIA NIH HHS/United States
GR  - K23 AG030967-01A1/AG/NIA NIH HHS/United States
GR  - K12 AG000294/AG/NIA NIH HHS/United States
GR  - P50 AG005134-268380/AG/NIA NIH HHS/United States
GR  - P01 AG004390/AG/NIA NIH HHS/United States
GR  - P01 AG004390-25/AG/NIA NIH HHS/United States
GR  - P50 AG005134/AG/NIA NIH HHS/United States
GR  - K23 AG030967/AG/NIA NIH HHS/United States
GR  - AG004390/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PL  - England
TA  - Clin Sci (Lond)
JT  - Clinical science (London, England : 1979)
JID - 7905731
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Siderophores)
RN  - 0 (Vasodilator Agents)
RN  - J06Y7MXW4D (Deferoxamine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Blood Flow Velocity
MH  - Blood Pressure/physiology
MH  - Cerebrovascular Circulation
MH  - Cross-Over Studies
MH  - Deferoxamine/*pharmacology
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Hypoxia-Inducible Factor 1/*drug effects/metabolism
MH  - Male
MH  - Middle Aged
MH  - Neuroprotective Agents/*pharmacology
MH  - Siderophores/*pharmacology
MH  - Tilt-Table Test
MH  - Vasodilation/drug effects
MH  - Vasodilator Agents/*pharmacology
MH  - Young Adult
PMC - PMC2854553
MID - NIHMS190309
EDAT- 2008/11/19 09:00
MHDA- 2009/08/01 09:00
PMCR- 2010/04/14
CRDT- 2008/11/19 09:00
PHST- 2008/11/19 09:00 [pubmed]
PHST- 2009/08/01 09:00 [medline]
PHST- 2008/11/19 09:00 [entrez]
PHST- 2010/04/14 00:00 [pmc-release]
AID - CS20080320 [pii]
AID - 10.1042/CS20080320 [doi]
PST - ppublish
SO  - Clin Sci (Lond). 2009 May;116(10):771-9. doi: 10.1042/CS20080320.