| Isoflurane preconditioning decreases myocardial infarction in rabbits via up-regulation of hypoxia inducible factor 1 that is mediated by mammalian target of rapamycin. | |
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MedLine Citation:
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PMID: 18292679 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Volatile anesthetics are known to protect the heart against ischemia-reperfusion injury. The authors tested whether anesthetic preconditioning with isoflurane is mediated via activation of the transcription factor hypoxia inducible factor 1 (HIF-1) and evaluated the role of mammalian target of rapamycin signaling in this process. METHODS: New Zealand White rabbits subjected to 40 min of regional myocardial ischemia, followed by 180 min of reperfusion, were assigned to the following groups: ischemia and reperfusion (I/R) only, isoflurane (1 minimal alveolar concentration) preconditioning, and isoflurane preconditioning in the presence of the mammalian target of rapamycin inhibitor rapamycin (0.25 mg/kg). Sham-operated, isoflurane + sham, rapamycin + sham, rapamycin + I/R, and dimethyl sulfoxide + I/R groups were also included. Creatine kinase-MB levels were assessed as an indicator of myocardial damage, and infarct size was evaluated by triphenyl tetrazolium chloride staining. HIF-1alpha expression and DNA binding were assessed by Western blotting and electrophoretic mobility shift analysis, respectively. RESULTS: Isoflurane preconditioning reduced infarct size compared with the I/R group: 26 +/- 4% versus 44 +/- 6% (P < 0.05). Creatine kinase-MB concentrations in the preconditioned animals (103 +/- 8% above baseline) were lower than in the I/R group (243 +/- 12% above baseline; P < 0.05). Rapamycin inhibited the cardioprotective effect of isoflurane: myocardial infarction increased to 44 +/- 4% and creatine kinase-MB level increased to 254 +/- 9% above baseline. HIF-1alpha protein expression and DNA binding activity increased after isoflurane preconditioning compared with the ischemia group. These effects were also inhibited by rapamycin. CONCLUSIONS: The current results indicate that isoflurane-induced myocardial protection involves activation of the HIF-1 pathway that is mediated by the mammalian target of rapamycin. |
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Authors:
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Jacob Raphael; Zhiyi Zuo; Suzan Abedat; Ronen Beeri; Yaacov Gozal |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Anesthesiology Volume: 108 ISSN: 1528-1175 ISO Abbreviation: Anesthesiology Publication Date: 2008 Mar |
Date Detail:
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Created Date: 2008-02-22 Completed Date: 2008-03-12 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 1300217 Medline TA: Anesthesiology Country: United States |
Other Details:
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Languages: eng Pagination: 415-25 Citation Subset: AIM; IM |
Affiliation:
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Department of Anesthesiology, University of Virginia Health Sciences System, Charlottesville, Virginia 22908, USA. jr5ef@virginia.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Hypoxia-Inducible Factor 1 / biosynthesis*, genetics, metabolism Ischemic Preconditioning, Myocardial / methods* Isoflurane / pharmacology, therapeutic use* Male Myocardial Infarction / metabolism*, prevention & control Protein Kinases / genetics, physiology* Rabbits Up-Regulation / drug effects, physiology* |
| Chemical | |
Reg. No./Substance:
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0/Hypoxia-Inducible Factor 1; 26675-46-7/Isoflurane; EC 2.7.-/Protein Kinases; EC 2.7.1.-/mTOR protein |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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