Linked Life Data

11273934

Source:http://linkedlifedata.com/resource/pubmed/id/11273934

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2001-3-29
pubmed:abstractText
Sepsis causes impairment of diaphragmatic contractility and endurance capacity. Nitric oxide (NO) produced via inducible NO synthase (iNOS) has been implicated in the pathogenesis. Peroxynitrite, a NO-derived powerful oxidant, may be responsible for infection-induced diaphragmatic muscle failure. Therefore, we examined whether ONO1714, a new selective iNOS inhibitor, prevents sepsis-induced diaphragmatic dysfunction. Fifty male Golden-Syrian hamsters were randomly divided into five groups: hamsters that underwent sham laparotomy alone and received saline injection (Group Sham), those that underwent cecal ligation with puncture (CLP) and received saline injection (Group Sepsis), those that underwent sham laparotomy and received injection of ONO1714 0.3 mg/kg (Group Sham-ONO1714high), those that underwent CLP and received ONO1714 0.1 mg/kg (Group Sepsis-ONO1714low), and those that underwent CLP and received ONO1714 0.3 mg/kg (Group Sepsis-ONO1714high). ONO1714 or saline was intraperitoneally injected 10 min before surgery. Diaphragmatic contractility was assessed in vitro using diaphragm muscle strips excised 24 h after operation. Diaphragm fatigability was assessed by time until tension decreased to 50% of the initial value (T50%) during fatigue trials. Twitch, tetanic tensions, and T50% during fatigue trials were reduced in Group Sepsis. Pretreatment with ONO1714 dose-dependently attenuated sepsis-induced diaphragmatic contractile profiles and endurance capacity. CLP increased plasma nitrite/nitrate (NOx; stable NO metabolites), and diaphragm malondialdehyde (MDA; a product of lipid peroxidation), positive immunostaining for nitrotyrosine (peroxynitrite footprint), and iNOS activity. ONO1714 attenuated the increase. This beneficial effect of ONO1714 may be attributable, in part, to inhibition of peroxynitrite-induced lipid peroxidation in the diaphragm. IMPLICATIONS: Sepsis impairs diaphragmatic contractility and endurance capacity, which may be involved in acute respiratory failure. Pretreatment with ONO1714, a new selective inducible nitric oxide synthase inhibitor, attenuated sepsis-induced diaphragmatic dysfunction in hamsters.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0003-2999
pubmed:author
pubmed:issnType
Print
pubmed:volume
92
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
959-66
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
ONO1714, a new inducible nitric oxide synthase inhibitor, attenuates sepsis-induced diaphragmatic dysfunction in hamsters.
pubmed:affiliation
Departments of Anaesthesiology and Intensive Care Unit, Kobe University School of Medicine, Kobe, Japan.
pubmed:publicationType
Journal Article, In Vitro