title: Brief periods of nitric oxide inhalation protect against myocardial ischemia-reperfusion injury.
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 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.
authors.affiliation: Anesthesia Center for Critical Care Research, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Nagasaka
authors.forename: Bernadette O
authors.initials: BO
authors.lastname: Fernandez
authors.forename: Maria F
authors.initials: MF
authors.lastname: Garcia-Saura
authors.forename: Bodil
authors.initials: B
authors.lastname: Petersen
authors.forename: Fumito
authors.initials: F
authors.lastname: Ichinose
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Bloch
authors.forename: Martin
authors.initials: M
authors.lastname: Feelisch
authors.forename: Warren M
authors.initials: WM
authors.lastname: Zapol
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D004912:Erythrocytes / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D009569:Nitric Oxide