ナガサカ　ヤスコ   NAGASAKA Yasuko   長坂　安子    所属   医学部 医学科（東京女子医科大学病院）    職種   教授・基幹分野長
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Brief periods of nitric oxide inhalation protect against myocardial ischemia-reperfusion injury.
掲載誌名	正式名：Anesthesiology 略　 称：Anesthesiology ISSNコード：15281175/00033022
掲載区分	国外
巻・号・頁	109(4),pp.675-82
国際共著	国際共著
著者・共著者	Nagasaka Yasuko, Fernandez Bernadette O, Garcia-Saura Maria F, Petersen Bodil, Ichinose Fumito, Bloch Kenneth D, Feelisch Martin, Zapol Warren M
担当区分	筆頭著者
発行年月	2008/10
概要	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.
DOI	10.1097/ALN.0b013e318186316e
PMID	18813047