Document Detail


Human adaptation to ischemia by preconditioning or unstable angina: involvement of nuclear factor kappa B, but not hypoxia-inducible factor 1 alpha in the heart.
MedLine Citation:
PMID:  18842422     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Ischemic preconditioning reduces infarct size and improves hemodynamic function. Unstable angina may be a clinical analogue to ischemic preconditioning, and involve activation of gene programs. We hypothesized that preceding unstable angina and/or ischemic preconditioning activated genes regulated by nuclear factor kappa B (NFkappaB) or hypoxia-inducible factor 1 alpha in parallel to improved cardiac function. METHODS: Patients undergoing coronary artery bypass grafting with stable or unstable angina were subjected to ischemic preconditioning or sham treatment (n=10-11 in each group). Central hemodynamics were monitored. Left ventricular and atrial biopsies were harvested before cardioplegic arrest and after 25 min of reperfusion. Expression of heat shock protein 72 was evaluated by immunoblot, and activation of NFkappaB was detected by electrophoretic mobility shift assay. Real-time PCR was used to quantify expression of genes regulated by NFkappaB (inducible nitric oxide synthase, tumor necrosis factor-alpha, intercellular adhesion molecule 1) or by hypoxia-inducible factor 1 alpha (heme oxygenase-1, glucose transporter-1 and vascular endothelial growth factor-A). RESULTS: Ischemic preconditioning improved postoperative cardiac index and left ventricular stroke work index in both stable and unstable groups on the first postoperative day. Expression of hypoxia-inducible factor 1 alpha regulated genes was not influenced by cardioplegia and reperfusion, ischemic preconditioning or unstable angina. Expression of the NFkappaB-regulated genes increased after cardioplegia and reperfusion, but this was not influenced by ischemic preconditioning in stable patients. Inducible nitric oxide synthase and tumor necrosis factor expression were reduced after ischemic preconditioning in patients with unstable angina. There were no significant differences in gene expression between stable and unstable patients before cardioplegia and ischemic preconditioning. NFkappaB translocation at reperfusion was reduced in stable preconditioned and unstable control patients compared to stable controls. Heat shock protein 72 expression increased after preconditioning of unstable patients. CONCLUSION: Cardiac function was improved by ischemic preconditioning in both stable and unstable patients. Unstable angina per se had no effect. NFkappaB-regulated genes were influenced by ischemic preconditioning, but hypoxia-inducible genes were not.
Authors:
Gabor Czibik; Zhongkai Wu; Gabrielle Paulsson Berne; Matti Tarkka; Jarle Vaage; Jari Laurikka; Otso Järvinen; Guro Valen
Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2008-10-07
Journal Detail:
Title:  European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery     Volume:  34     ISSN:  1873-734X     ISO Abbreviation:  Eur J Cardiothorac Surg     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-12-10     Completed Date:  2009-03-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8804069     Medline TA:  Eur J Cardiothorac Surg     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  976-84     Citation Subset:  IM    
Affiliation:
Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway. gaborc@medisin.uio.no
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MeSH Terms
Descriptor/Qualifier:
Aged
Angina, Unstable / genetics,  metabolism*,  surgery
Cardiopulmonary Bypass / methods
Coronary Artery Bypass / methods*
Female
Gene Expression Regulation / physiology
Hemodynamics
Humans
Hypoxia-Inducible Factor 1 / genetics,  physiology*
Ischemic Preconditioning, Myocardial / methods*
Male
Middle Aged
NF-kappa B / genetics,  physiology*
Reverse Transcriptase Polymerase Chain Reaction
Treatment Outcome
Chemical
Reg. No./Substance:
0/Hypoxia-Inducible Factor 1; 0/NF-kappa B

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


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