Document Detail

Protection of the right ventricle from ischemia and reperfusion by preceding hypoxia.
MedLine Citation:
PMID:  18488199     Owner:  NLM     Status:  MEDLINE    
We have previously shown that 2 weeks of hypoxia protect the right ventricle of the rat heart from subsequent ischemia and reperfusion (I/R). In the present study, we examined the following: (1) Do shorter periods of hypoxia protect from subsequent I/R? (2) Does intermittent normoxia increase the cardioprotective effect? (3) Is hypoxia-inducible factor-1alpha (HIF-1alpha), erythropoietin (EPO), or vascular endothelial growth factor (VEGF) involved in the protective effects? Preischemic cardiac work was followed by global ischemia, reperfusion, and postischemic cardiac work (15 min each). External heart work was determined at the end of both work phases. Four groups of hearts were investigated: hearts from normoxic rats (n=8), hearts from rats after 24 h of continuous hypoxia (10.5% inspired oxygen, n=7), hearts from rats after 24 h hypoxia with a single intermission of 30 min normoxia (n=9), and hearts from rats after 24 h hypoxia and multiple intermissions of 30 min normoxia (n=7). Protein levels of HIF-1alpha and mRNA levels of EPO and VEGF were determined in right ventricular tissue of normoxic and hypoxic hearts. Postischemic right heart recovery was better in all three hypoxic groups compared with normoxic hearts (61.8 +/- 5.9%, 65.6 +/- 3.0%, and 75.7 +/- 2.6% vs. 46.0 +/- 3.9%, p < 0.01). Hypoxia with multiple normoxic intermissions further improved right heart recovery compared to continuous hypoxia (p < 0.05). HIF-1alpha protein levels were 80.3 +/- 2.5 pg/microg in normoxic hearts and 108.0 +/- 10.3 pg/microg in hypoxic hearts (p = 0.02). No differences in EPO and VEGF mRNA levels were found between normoxic and hypoxic hearts. Twenty-four hours of continuous hypoxia protect the isolated working right heart from subsequent ischemia and reperfusion. When preceding hypoxia is interrupted by multiple reoxygenation periods, there is a further significant increase in cardiac functional recovery. HIF-1alpha may be involved in the protective effect.
Daniela Wasserfuhr; Sürreya M Cetin; Jun Yang; Patricia Freitag; Stilla Frede; Heinz Jakob; Parwis Massoudy
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Publication Detail:
Type:  Journal Article     Date:  2008-05-17
Journal Detail:
Title:  Naunyn-Schmiedeberg's archives of pharmacology     Volume:  378     ISSN:  0028-1298     ISO Abbreviation:  Naunyn Schmiedebergs Arch. Pharmacol.     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-06-19     Completed Date:  2008-12-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0326264     Medline TA:  Naunyn Schmiedebergs Arch Pharmacol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  27-32     Citation Subset:  IM    
Department of Thoracic and Cardiovascular Surgery, West German Heart Center Essen, University Hospital Essen, Hufelandstr. 55, 45417, Essen, Germany.
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MeSH Terms
Anoxia / metabolism*
Erythropoietin / metabolism
Heart Ventricles / physiopathology
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
Ischemic Preconditioning, Myocardial / methods*
Oxygen / metabolism
RNA, Messenger / metabolism
Rats, Wistar
Reperfusion Injury / physiopathology,  prevention & control*
Time Factors
Vascular Endothelial Growth Factor A / metabolism
Reg. No./Substance:
0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/RNA, Messenger; 0/Vascular Endothelial Growth Factor A; 11096-26-7/Erythropoietin; 7782-44-7/Oxygen

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