Document Detail


Desferrioxamine elevates pulmonary vascular resistance in humans: potential for involvement of HIF-1.
MedLine Citation:
PMID:  12015365     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hypoxia-inducible factor (HIF)-1 is stabilized by hypoxia and iron chelation. We hypothesized that HIF-1 might be involved in pulmonary vascular regulation and that infusion of desferrioxamine over 8 h would consequently mimic hypoxia and elevate pulmonary vascular resistance. In study A, we characterized the pulmonary vascular response to 4 h of isocapnic hypoxia; in study B, we measured the pulmonary vascular response to 8 h of desferrioxamine infusion. For study A, 11 volunteers undertook two protocols: 1) 4 h of isocapnic hypoxia (end-tidal PO(2) = 50 Torr), followed by 2 h of recovery with isocapnic euoxia (end-tidal PO(2) = 100 Torr), and 2) 6 h of air breathing (control). For study B, nine volunteers undertook two protocols while breathing air: 1) continuous infusion of desferrioxamine (4 g/70 kg) over 8 h and 2) continuous infusion of saline over 8 h (control). In both studies, pulmonary vascular resistance was assessed at 0.5- to 1-h intervals by Doppler echocardiography via the maximum pressure gradient during systole across the tricuspid valve. Results show a progressive rise in pressure gradient over the first 3-4 h with both isocapnic hypoxia (P < 0.001) and desferrioxamine infusion (P < 0.005) to increases of ~16 and 4 Torr, respectively. These results support a role for HIF-regulated gene activation in human hypoxic pulmonary vasoconstriction.
Authors:
George M Balanos; Keith L Dorrington; Peter A Robbins
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of applied physiology (Bethesda, Md. : 1985)     Volume:  92     ISSN:  8750-7587     ISO Abbreviation:  J. Appl. Physiol.     Publication Date:  2002 Jun 
Date Detail:
Created Date:  2002-05-16     Completed Date:  2002-10-23     Revised Date:  2013-09-26    
Medline Journal Info:
Nlm Unique ID:  8502536     Medline TA:  J Appl Physiol (1985)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2501-7     Citation Subset:  IM    
Affiliation:
University Laboratory of Physiology, University of Oxford, Parks Road, Oxford OX1 3PT, United Kingdom.
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MeSH Terms
Descriptor/Qualifier:
Anoxia / physiopathology
Cardiac Output / drug effects
DNA-Binding Proteins / physiology*
Deferoxamine / pharmacology*
Echocardiography
Female
Heart Rate / drug effects
Humans
Hypoxia-Inducible Factor 1
Hypoxia-Inducible Factor 1, alpha Subunit
Iron Chelating Agents / pharmacology*
Male
Nuclear Proteins / physiology*
Pulmonary Circulation / drug effects*,  physiology*
Stroke Volume / drug effects
Transcription Factors*
Vascular Resistance / drug effects*,  physiology*
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/HIF1A protein, human; 0/Hypoxia-Inducible Factor 1; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/Iron Chelating Agents; 0/Nuclear Proteins; 0/Transcription Factors; 70-51-9/Deferoxamine

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