Abstract:
BACKGROUND AND OBJECTIVES:In isolated-perfused lungs of lipopolysaccharide (LPS)-challenged rats, vasodilatation to inhaled nitric oxide (NO) is impaired. Inhibition of nitric oxide synthase 2 (NOS2) by aminoguanidine (AG) prevented hyporesponsiveness to inhaled NO. Here, we investigated whether NOS2-mediated nitrite/nitrate synthesis modulates responsiveness to inhaled NO. METHODS:Sprague-Dawley rats received intraperitoneally 0.5 mg kg(-1) LPS. Four hours later, LPS-treated rats received 3, 10 or 30 mg kg(-1) AG or 0.01, 0.1 or 1 mg kg(-1) S-methylisothiourea (SMT) by intraperitoneal injection. Sixteen to eighteen hours later, lungs were isolated and perfused, and pulmonary artery pressure (PAP) was elevated by 6-8 mmHg using the thromboxane analogue U46619. The decrease of PAP in response to inhaled NO and nitrate/nitrite levels in serum and perfusate was measured. RESULTS:In rats treated with LPS alone or 0.01 or 0.1 mg kg(-1) SMT, 40 ppm NO decreased PAP less than in rats treated with AG and 1 mg kg(-1) SMT (-1.8 mmHg (95% confidence interval: -1.5 to -2.1) vs. -6.0 mmHg (-5.7 to -6.3), P < 0.01). Improved NO responsiveness was associated with lower serum and perfusate nitrite/nitrate levels than in rats with hyporesponsiveness to inhaled NO (102 micromol (82-122) vs. 282 micromol (261-303) and 8.1 micromol (6.9-9.3) vs. 19.8 micromol (17.2-22.4), respectively, P < 0.01). CONCLUSIONS:These observations demonstrate that in isolated-perfused lungs of LPS-treated rats, NOS2 inhibition improved responsiveness to inhaled NO. Here, responsiveness to inhaled NO is dependent on the ability of NOS2 inhibitors to reduce nitrite and nitrate levels in serum and released in the lung.
journal_name
Eur J Anaesthesioljournal_title
European journal of anaesthesiologyauthors
Bopp Ch,Gust R,Taut F,Gries A,Martin E,Klein Adoi
10.1017/S0265021506001463subject
Has Abstractpub_date
2007-04-01 00:00:00pages
362-9issue
4eissn
0265-0215issn
1365-2346pii
S0265021506001463journal_volume
24pub_type
杂志文章abstract:BACKGROUND AND OBJECTIVE:Most therapeutic options for postoperative delirium are only symptom oriented; therefore, the best approach remains prevention. The aim of this study was to identify predisposing and precipitating factors for early postoperative delirium. METHODS:A total of 1002 patients were screened for deli...
journal_title:European journal of anaesthesiology
pub_type: 杂志文章
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更新日期:2010-05-01 00:00:00
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journal_title:European journal of anaesthesiology
pub_type: 杂志文章,多中心研究,随机对照试验
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journal_title:European journal of anaesthesiology
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pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1991-05-01 00:00:00
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更新日期:1998-03-01 00:00:00
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