Document Detail

The mechanism of helium-induced preconditioning: a direct role for nitric oxide in rabbits.
MedLine Citation:
PMID:  18713880     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Helium produces preconditioning against myocardial infarction by activating prosurvival signaling, but whether nitric oxide (NO) generated by endothelial NO synthase plays a role in this phenomenon is unknown. We tested the hypothesis that NO mediates helium-induced cardioprotection in vivo. METHODS: Rabbits (n = 62) instrumented for hemodynamic measurement were subjected to a 30-min left anterior descending coronary artery occlusion and 3 h reperfusion, and received 0.9% saline (control) or three cycles of 70% helium-30% oxygen administered for 5 min interspersed with 5 min of an air-oxygen mixture before left anterior descending coronary artery occlusion in the absence or presence of pretreatment with the nonselective NOS inhibitor N-nitro-l-arginine methyl ester (L-NAME; 10 mg/kg), the selective inducible NOS inhibitor aminoguanidine hydrochloride (AG; 300 mg/kg), or selective neuronal NOS inhibitor 7-nitroindazole (7-NI; 50 mg/kg). In additional rabbits, the fluorescent probe 4,5-diaminofluroscein diacetate (DAF-2DA) and confocal laser microscopy were used to detect NO production in the absence or presence of helium with or without L-NAME pretreatment. RESULTS: Helium reduced (P < 0.05) infarct size (24% +/- 4% of the left ventricular area at risk; mean +/- sd) compared with control (46% +/- 3%). L-NAME, AG, and 7-NI did not alter myocardial infarct size when administered alone. L-NAME, but not 7-NI or AG, abolished helium-induced cardioprotection. Helium enhanced DAF-2DA fluorescence compared with control (26 +/- 8 vs 15 +/- 5 U, respectively). Pretreatment with L-NAME abolished these helium-induced increases in DAF-2DA fluorescence. CONCLUSIONS: The results indicate that cardioprotection by helium is mediated by NO that is probably generated by endothelial NOS in vivo.
Paul S Pagel; John G Krolikowski; Phillip F Pratt; Yon Hee Shim; Julien Amour; David C Warltier; Dorothee Weihrauch
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anesthesia and analgesia     Volume:  107     ISSN:  1526-7598     ISO Abbreviation:  Anesth. Analg.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-08-20     Completed Date:  2008-09-11     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  1310650     Medline TA:  Anesth Analg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  762-8     Citation Subset:  AIM; IM    
Department of Anesthesiology, Medical College of Wisconsin, Clement J. Zablocki Veterans Affairs Medical Center, Anesthesia Service, 5000 W. National Ave., Milwaukee, WI 53295, USA.
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MeSH Terms
Cardiotonic Agents / pharmacology*
Enzyme Inhibitors / pharmacology
Fluorescein / pharmacology
Helium / pharmacology*
Indazoles / pharmacology
Indicators and Reagents / pharmacology
Ischemic Preconditioning, Myocardial*
Microscopy, Confocal / methods
NG-Nitroarginine Methyl Ester / pharmacology
Nitric Oxide / metabolism*
Nitric Oxide Synthase Type III / metabolism*
Grant Support
GM 066730/GM/NIGMS NIH HHS; HL 054820/HL/NHLBI NIH HHS; P01 GM066730-040001/GM/NIGMS NIH HHS; R01 HL054820-11/HL/NHLBI NIH HHS
Reg. No./Substance:
0/4,5-diaminofluorescein diacetate; 0/Cardiotonic Agents; 0/Enzyme Inhibitors; 0/Indazoles; 0/Indicators and Reagents; 10102-43-9/Nitric Oxide; 2321-07-5/Fluorescein; 2942-42-9/7-nitroindazole; 50903-99-6/NG-Nitroarginine Methyl Ester; 7440-59-7/Helium; EC Oxide Synthase Type III

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

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