Document Detail

Role of Erk1/2, p70s6K, and eNOS in isoflurane-induced cardioprotection during early reperfusion in vivo.
MedLine Citation:
PMID:  16434759     Owner:  NLM     Status:  MEDLINE    
PURPOSE: Administration of isoflurane during early reperfusion after prolonged coronary artery occlusion decreases myocardial infarct size by activating phosphatidylinositol-3-kinase (PI3K) signal transduction. The extracellular signal-related kinases (Erk1/2) represent a redundant mechanism by which signaling elements downstream from PI3K, including 70-kDA ribosomal protein s6 kinase (p70s6K) and endothelial nitric oxide synthase (eNOS), may be activated to reduce reperfusion injury. We tested the hypothesis Erk1/2, p70s6K, and eNOS mediate isoflurane-induced postconditioning in rabbit myocardium in vivo.
METHODS: Barbiturate-anesthetized rabbits (n = 78) instrumented for measurement of systemic hemodynamics were subjected to a 30-min coronary occlusion followed by three hours reperfusion. Rabbits were randomly assigned to receive 0.9% saline (control), the Erk1/2 inhibitor PD 098059 (2 mg x kg(-1)), the p70s6K inhibitor rapamycin (0.25 mg x kg(-1)), the nonselective nitric oxide synthase (NOS) inhibitor N-nitro-L-arginine methyl ester (L-NAME; 10 mg x kg(-1)), the selective inducible NOS antagonist aminoguanidine hydrochloride (AG, 300 mg x kg(-1)), or the selective neuronal NOS inhibitor 7-nitroindazole (7-NI, 50 mg x kg(-1)) in the presence or absence of 1.0 minimum alveolar concentration isoflurane administered for three minutes before and two minutes after reperfusion.
RESULTS: Brief exposure to 1.0 minimum alveolar concentration isoflurane reduced (P < 0.05) infarct size (21 +/- 4% [mean +/- SD] of left ventricle area at risk, respectively; triphenyltetrazolium staining) as compared to control (41 +/- 5%). PD 098059, rapamycin, and L-NAME, but not AG nor 7-NI, abolished the protection produced by isoflurane.
CONCLUSION: The results suggest that the protective effects of isoflurane against infarction during early reperfusion are mediated by Erk1/2, p70s6K, and eNOS in vivo.
John G Krolikowski; Dorothee Weihrauch; Martin Bienengraeber; Judy R Kersten; David C Warltier; Paul S Pagel
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Canadian journal of anaesthesia = Journal canadien d'anesthésie     Volume:  53     ISSN:  0832-610X     ISO Abbreviation:  Can J Anaesth     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-01-25     Completed Date:  2006-06-28     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  8701709     Medline TA:  Can J Anaesth     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  174-82     Citation Subset:  IM    
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
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MeSH Terms
Anesthetics, Inhalation / pharmacology*
Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors,  metabolism*
Flavonoids / pharmacology
Ischemic Preconditioning, Myocardial*
Isoflurane / pharmacology*
Myocardial Reperfusion Injury / metabolism,  prevention & control*
NG-Nitroarginine Methyl Ester / pharmacology
Nitric Oxide Synthase Type III / antagonists & inhibitors,  metabolism*
Ribosomal Protein S6 Kinases, 70-kDa / antagonists & inhibitors,  metabolism*
Sirolimus / pharmacology
Grant Support
Reg. No./Substance:
0/2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; 0/Anesthetics, Inhalation; 0/Flavonoids; 26675-46-7/Isoflurane; 50903-99-6/NG-Nitroarginine Methyl Ester; 53123-88-9/Sirolimus; EC Oxide Synthase Type III; EC Protein S6 Kinases, 70-kDa; EC Signal-Regulated MAP Kinases

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

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