Document Detail

Brief periods of nitric oxide inhalation protect against myocardial ischemia-reperfusion injury.
MedLine Citation:
PMID:  18813047     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Prolonged breathing of nitric oxide reduces myocardial ischemia-reperfusion injury, but the precise mechanisms responsible for the cardioprotective effects of inhaled nitric oxide are incompletely understood. METHODS: The authors investigated the fate of inhaled nitric oxide (80 parts per million) in mice and quantified the formation of nitric oxide metabolites in blood and tissues. The authors tested whether the accumulation of nitric oxide metabolites correlated with the ability of inhaled nitric oxide to protect against cardiac ischemia-reperfusion injury. RESULTS: Mice absorbed nitric oxide in a nearly linear fashion (0.19 +/- 0.02 micromol/g x h). Breathing nitric oxide rapidly increased a broad spectrum of nitric oxide metabolites. Levels of erythrocytic S-nitrosothiols, N-nitrosamines, and nitrosyl-hemes increased dramatically within 30 s of commencing nitric oxide inhalation. Marked increases of lung S-nitrosothiol and liver N-nitrosamine levels were measured, as well as elevated cardiac and brain nitric oxide metabolite levels. Breathing low oxygen concentrations potentiated the ability of inhaled nitric oxide to increase cardiac nitric oxide metabolite levels. Concentrations of each nitric oxide metabolite, except nitrate, rapidly reached a plateau and were similar after 5 and 60 min. In a murine cardiac ischemia-reperfusion injury model, breathing nitric oxide for either 5 or 60 min before reperfusion decreased myocardial infarction size as a fraction of myocardial area at risk by 31% or 32%, respectively. CONCLUSIONS: Breathing nitric oxide leads to the rapid accumulation of a variety of nitric oxide metabolites in blood and tissues, contributing to the ability of brief periods of nitric oxide inhalation to provide cardioprotection against ischemia-reperfusion injury. The nitric oxide metabolite concentrations achieved in a target tissue may be more important than the absolute amounts of nitric oxide absorbed.
Yasuko Nagasaka; Bernadette O Fernandez; Maria F Garcia-Saura; Bodil Petersen; Fumito Ichinose; Kenneth D Bloch; Martin Feelisch; Warren M Zapol
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Anesthesiology     Volume:  109     ISSN:  1528-1175     ISO Abbreviation:  Anesthesiology     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-09-24     Completed Date:  2008-10-07     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  1300217     Medline TA:  Anesthesiology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  675-82     Citation Subset:  AIM; IM    
Anesthesia Center for Critical Care Research, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
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MeSH Terms
Administration, Inhalation
Anoxia / metabolism
Erythrocytes / metabolism
Mice, Inbred C57BL
Myocardial Reperfusion Injury / prevention & control*
Nitric Oxide / administration & dosage*,  pharmacokinetics
Grant Support
Reg. No./Substance:
10102-43-9/Nitric Oxide
Comment In:
Anesthesiology. 2009 May;110(5):1198-9   [PMID:  19387197 ]

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

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