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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, 109, (4), pp. 675-682. (doi:10.1097/ALN.0b013e318186316e). (PMID:18813047).

Record type: Article


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 ?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 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

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Published date: October 2008
Organisations: Clinical & Experimental Sciences


Local EPrints ID: 337707
ISSN: 0003-3022
PURE UUID: 5fe6d641-5794-4790-9b8f-4fbd97775ac5
ORCID for Martin Feelisch: ORCID iD

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Date deposited: 02 May 2012 13:09
Last modified: 18 Jul 2017 06:01

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Author: Yasuko Nagasaka
Author: Bernadette O. Fernandez
Author: Maria F. Garcia-Saura
Author: Bodil Petersen
Author: Fumito Ichinose
Author: Kenneth D. Bloch
Author: Martin Feelisch ORCID iD
Author: Warren M. Zapol

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