| The mechanism of helium-induced preconditioning: a direct role for nitric oxide in rabbits. | |
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MedLine Citation:
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PMID: 18713880 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Paul S Pagel; John G Krolikowski; Phillip F Pratt; Yon Hee Shim; Julien Amour; David C Warltier; Dorothee Weihrauch |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Anesthesia and analgesia Volume: 107 ISSN: 1526-7598 ISO Abbreviation: Anesth. Analg. Publication Date: 2008 Sep |
Date Detail:
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Created Date: 2008-08-20 Completed Date: 2008-09-11 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 1310650 Medline TA: Anesth Analg Country: United States |
Other Details:
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Languages: eng Pagination: 762-8 Citation Subset: AIM; IM |
Affiliation:
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Department of Anesthesiology, Medical College of Wisconsin, Clement J. Zablocki Veterans Affairs Medical Center, Anesthesia Service, 5000 W. National Ave., Milwaukee, WI 53295, USA. pspagel@mcw.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cardiotonic Agents / pharmacology* Enzyme Inhibitors / pharmacology Fluorescein / pharmacology Helium / pharmacology* Hemodynamics Indazoles / pharmacology Indicators and Reagents / pharmacology Ischemic Preconditioning, Myocardial* Male Microscopy, Confocal / methods NG-Nitroarginine Methyl Ester / pharmacology Nitric Oxide / metabolism* Nitric Oxide Synthase Type III / metabolism* Rabbits |
| Grant Support | |
ID/Acronym/Agency:
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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 |
| Chemical | |
Reg. No./Substance:
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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 1.14.13.39/Nitric Oxide Synthase Type III |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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