Document Detail


Hyperglycemia inhibits anesthetic-induced postconditioning in the rabbit heart via modulation of phosphatidylinositol-3-kinase/Akt and endothelial nitric oxide synthase signaling.
MedLine Citation:
PMID:  20125034     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hyperglycemia is known to inhibit ischemic and anesthetic preconditioning. We tested whether hyperglycemia inhibits anesthetic postconditioning with isoflurane and whether this effect is mediated via phosphatidylinositol-3-kinase/Akt and nitric oxide signaling. New Zealand white rabbits subjected to 40 minutes of myocardial ischemia, followed by 3 hours of reperfusion were assigned to the following groups: ischemia and reperfusion (I/R), isoflurane (1 minimal alveolar concentration) postconditioning, and isoflurane postconditioning with hyperglycemia (15% dextrose in water infusion). A control group of hyperglycemia + I/R was also included. Levels of MB fraction of creatine kinase (CK-MB) were assessed as an indicator of myocardial damage, and infarct size was evaluated. Akt, iNOS, and endothelial nitric oxide synthase (eNOS) expression was assessed by immunoblotting. Determination of nitrite and nitrate levels in the myocardium was also performed. Isoflurane postconditioning reduced infarct size compared with the I/R group: 25% +/- 4% versus 49% +/- 5% (P < 0.01). CK-MB concentrations in the postconditioned animals (124% +/- 14% above baseline levels) were lower than those in the I/R group (236% +/- 9% above baseline levels; P < 0.01). Hyperglycemia inhibited the cardioprotective effect of isoflurane: myocardial infarction size was 46% +/- 4% and CK-MB increased to 241% +/- 11% above baseline. Phosphorylated Akt and eNOS protein expression increased after isoflurane postconditioning compared with the I/R group. These effects were also inhibited by hyperglycemia. iNOS expression, however, did not change significantly within the various experimental groups. There were increased tissue levels of nitrite and nitrate (NO(x)) in the postconditioning group. This was also blocked by hyperglycemia. Our results suggest that hyperglycemia inhibits cardioprotection provided by isoflurane postconditioning. This effect seems to be mediated via modulation Akt and eNOS.
Authors:
Jacob Raphael; Yaacov Gozal; Nachum Navot; Zhiyi Zuo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  55     ISSN:  1533-4023     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-04-21     Completed Date:  2010-09-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  348-57     Citation Subset:  IM    
Affiliation:
Department of Anesthesiology, University of Virginia, Charlottesville, VA 22908, USA. jr5ef@virginia.edu
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MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase / metabolism*
Anesthetics / pharmacology,  therapeutic use*
Animals
Blood Glucose / drug effects,  metabolism
Blood Pressure / physiology
Creatine Kinase, MB Form / blood
Glucose / pharmacology
Heart / drug effects*
Heart Rate / drug effects,  physiology
Hyperglycemia / chemically induced,  complications*,  metabolism
Isoflurane / pharmacology,  therapeutic use
Male
Myocardial Infarction / pathology
Myocardial Reperfusion Injury / complications,  metabolism,  prevention & control*
Myocardium / metabolism,  pathology
Nitrates / metabolism
Nitric Oxide Synthase Type II / metabolism
Nitric Oxide Synthase Type III / metabolism*
Nitrites / metabolism
Phosphorylation / drug effects
Proto-Oncogene Proteins c-akt / metabolism*
Rabbits
Signal Transduction / drug effects,  physiology
Chemical
Reg. No./Substance:
0/Anesthetics; 0/Blood Glucose; 0/Nitrates; 0/Nitrites; 26675-46-7/Isoflurane; 50-99-7/Glucose; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.3.2/Creatine Kinase, MB Form

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


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