Document Detail


Effects of iron supplementation and depletion on hypoxic pulmonary hypertension: two randomized controlled trials.
MedLine Citation:
PMID:  19809026     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
CONTEXT: Hypoxia is a major cause of pulmonary hypertension in respiratory disease and at high altitude. Recent work has established that the effect of hypoxia on pulmonary arterial pressure may depend on iron status, possibly acting through the transcription factor hypoxia-inducible factor, but the pathophysiological and clinical importance of this interaction is unknown. OBJECTIVE: To determine whether increasing or decreasing iron availability modifies altitude-induced hypoxic pulmonary hypertension. DESIGN, SETTING, AND PARTICIPANTS: Two randomized, double-blind, placebo-controlled protocols conducted in October-November 2008. In the first protocol, 22 healthy sea-level resident men (aged 19-60 years) were studied over 1 week of hypoxia at Cerro de Pasco, Peru (altitude 4340 m). In the second protocol, 11 high-altitude resident men (aged 30-59 years) diagnosed with chronic mountain sickness were studied over 1 month of hypoxia at Cerro de Pasco, Peru. INTERVENTION: In the first protocol, participants received intravenous infusions of Fe(III)-hydroxide sucrose (200 mg) or placebo on the third day of hypoxia. In the second protocol, patients underwent staged isovolemic venesection of 2 L of blood. Two weeks later, patients received intravenous infusions of Fe(III)-hydroxide sucrose (400 mg) or placebo, which were subsequently crossed over. MAIN OUTCOME MEASURE: Effect of varying iron availability on pulmonary artery systolic pressure (PASP) assessed by Doppler echocardiography. RESULTS: In the sea-level resident protocol, approximately 40% of the pulmonary hypertensive response to hypoxia was reversed by infusion of iron, which reduced PASP by 6 mm Hg (95% confidence interval [CI], 4-8 mm Hg), from 37 mm Hg (95% CI, 34-40 mm Hg) to 31 mm Hg (95% CI, 29-33 mm Hg; P = .01). In the chronic mountain sickness protocol, progressive iron deficiency induced by venesection was associated with an approximately 25% increase in PASP of 9 mm Hg (95% CI, 4-14 mm Hg), from 37 mm Hg (95% CI, 30-44 mm Hg) to 46 mm Hg (95% CI, 40-52 mm Hg; P = .003). During the subsequent crossover period, no acute effect of iron replacement on PASP was detected. CONCLUSION: Hypoxic pulmonary hypertension may be attenuated by iron supplementation and exacerbated by iron depletion. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00952302.
Authors:
Thomas G Smith; Nick P Talbot; Catherine Privat; Maria Rivera-Ch; Annabel H Nickol; Peter J Ratcliffe; Keith L Dorrington; Fabiola León-Velarde; Peter A Robbins
Related Documents :
23933756 - Novel metabolic drugs and blood pressure: implications for the treatment of obese hyper...
3789196 - Function of myoglobin in oxygen consumption by isolated perfused fish hearts.
7092756 - Women at altitude: cardiovascular responses to hypoxia.
8184936 - Hypoxia stimulates release of anp and bnp from perfused rat ventricular myocardium.
18256576 - The frequency of elevated blood pressure in obese minority youth.
3804926 - Microvascular pressures measured by micropuncture in isolated perfused lamb lungs.
Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  JAMA : the journal of the American Medical Association     Volume:  302     ISSN:  1538-3598     ISO Abbreviation:  JAMA     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-10-07     Completed Date:  2009-10-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7501160     Medline TA:  JAMA     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1444-50     Citation Subset:  AIM; IM    
Affiliation:
Department of Physiology, Anatomy, and Genetics, University of Oxford, Sherrington Bldg, Parks Road, Oxford OX1 3PT, England.
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00952302
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adult
Altitude
Altitude Sickness / complications,  physiopathology*
Anoxia / physiopathology
Blood Pressure
Cross-Over Studies
Double-Blind Method
Echocardiography, Doppler
Ferric Compounds / administration & dosage,  pharmacology*
Humans
Hypertension, Pulmonary / etiology,  physiopathology*,  prevention & control,  ultrasonography
Iron / deficiency*
Male
Middle Aged
Phlebotomy
Pulmonary Artery
Systole
Young Adult
Grant Support
ID/Acronym/Agency:
//Wellcome Trust
Chemical
Reg. No./Substance:
0/Ferric Compounds; 1309-33-7/ferric hydroxide; 7439-89-6/Iron; 8047-67-4/ferric oxide, saccharated

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Using effectiveness and cost-effectiveness to make drug coverage decisions: a comparison of Britain,...
Next Document:  A-lines and B-lines: lung ultrasound as a bedside tool for predicting pulmonary artery occlusion pre...