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Brief periods of nitric oxide inhalation protect against myocardial ischemia-reperfusion injury

Brief periods of nitric oxide inhalation protect against myocardial ischemia-reperfusion injury
Brief periods of nitric oxide inhalation protect against myocardial ischemia-reperfusion injury
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
0003-3022
675-682
Nagasaka, Yasuko
059f8837-21bd-4075-adcd-883f98b8edbf
Fernandez, Bernadette O.
27babc73-7646-4908-86e2-6c29d79fb938
Garcia-Saura, Maria F.
a3df7c56-91cf-476d-8de8-ce31a42c13e4
Petersen, Bodil
6517418e-b58b-4a74-b413-47f8cfc15667
Ichinose, Fumito
aadeb0ff-b8e5-4bdb-9d5f-b4f17f937a59
Bloch, Kenneth D.
25d43ddf-77d4-448b-b618-079a0492aba1
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Zapol, Warren M.
84efe66d-166f-4b1d-8db2-b48586aea27e
Nagasaka, Yasuko
059f8837-21bd-4075-adcd-883f98b8edbf
Fernandez, Bernadette O.
27babc73-7646-4908-86e2-6c29d79fb938
Garcia-Saura, Maria F.
a3df7c56-91cf-476d-8de8-ce31a42c13e4
Petersen, Bodil
6517418e-b58b-4a74-b413-47f8cfc15667
Ichinose, Fumito
aadeb0ff-b8e5-4bdb-9d5f-b4f17f937a59
Bloch, Kenneth D.
25d43ddf-77d4-448b-b618-079a0492aba1
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Zapol, Warren M.
84efe66d-166f-4b1d-8db2-b48586aea27e

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

Record type: Article

Abstract

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

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Local EPrints ID: 337707
URI: http://eprints.soton.ac.uk/id/eprint/337707
ISSN: 0003-3022
PURE UUID: 5fe6d641-5794-4790-9b8f-4fbd97775ac5
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

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Date deposited: 02 May 2012 13:09
Last modified: 15 Mar 2024 03:41

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Contributors

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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