Brief periods of nitric oxide inhalation protect against myocardial ischemia-reperfusion injury
Nagasaka, Yasuko, Fernandez, Bernadette O., Garcia-Saura, Maria F., Petersen, Bodil, Ichinose, Fumito, Bloch, Kenneth D., Feelisch, Martin and Zapol, Warren M.. (2008) Brief periods of nitric oxide inhalation protect against myocardial ischemia-reperfusion injury. Anesthesiology, Vol.109 (No.4). pp. 675-682. ISSN 0003-3022Full text not available from this repository.
Official URL: http://dx.doi.org/10.1097/ALN.0b013e318186316e
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 die 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 mu mol/g (.) 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 die 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.
|Item Type:||Journal Article|
|Subjects:||R Medicine > RD Surgery|
|Divisions:||Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016)
Faculty of Medicine > Warwick Medical School
|Journal or Publication Title:||Anesthesiology|
|Publisher:||Lippincott Williams & Wilkins|
|Official Date:||October 2008|
|Number of Pages:||8|
|Page Range:||pp. 675-682|
|Access rights to Published version:||Restricted or Subscription Access|
|Funder:||National Institutes of Helath, Bethesda, Maryland, Massachusetts General Hospital, Boston, Massachusetts, and IKARIA, Clinton, New Jersey|
|Grant number:||HL07224, HL42397, DA020644, HL70896|
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