| Continuous infusion of sivelestat sodium hydrate prevents lipopolysaccharide-induced intestinal paralysis and hypotension in conscious guinea-pigs. | |
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MedLine Citation:
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PMID: 18346172 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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1. Sivelestat sodium hydrate (sivelestat), a neutrophil elastase inhibitor, is used to treat acute lung injury associated with systemic inflammatory response syndrome, but its effects have not been described for endotoxaemia. In the present study, we examined the effects of a continuous infusion of sivelestat on intestinal mechanical activity and blood pressure using an endotoxaemic model in conscious, unrestrained guinea-pigs. 2. Guinea-pigs underwent laparotomy while anaesthetized and were implanted with a force transducer sutured onto the taenia caecum. With this transducer, changes in tension in the intestinal longitudinal muscle were measured continuously via telemetry. Catheters were inserted into the carotid artery and jugular vein, were tunnelled subcutaneously and were accessed from the back of the neck. These catheters were connected to a cannula swivel and were used to monitor arterial pressure as well as to administer drugs i.v. in conscious, unrestrained guinea-pigs. Twenty hours after surgery, guinea-pigs received a single dose of lipopolysaccharide (LPS; 0.3 mg/kg, i.p.) 10 min after the start of a continuous 2 h i.v. infusion of sivelestat (30 mg/kg per h) or vehicle (saline). Elastase activity before and after sivelestat or vehicle administration was measured spectrometrically using a specific synthetic substrate. 3. We confirmed that intestinal longitudinal muscle tension decreased 2-3 h after LPS administration in the control group, with a concurrent decline in blood pressure. In guinea-pigs treated with sivelestat, the LPS-induced decreases in muscle tension and blood pressure were significantly reduced. In LPS-treated control guinea-pigs, serum elastase activity was elevated and this increase was significantly attenuated by administration of sivelestat. 4. The findings from the present study suggest that sivelstat can effectively reduce intestinal dysfunction and attenuate LPS-induced decreases in blood pressure in endotoxaemia. |
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Authors:
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Shunsuke Hara; Kayo Nemoto; Norifumi Ninomiya; Minoru Kubota; Masamune Kuno; Yasuhiro Yamamoto |
Publication Detail:
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Type: Comparative Study; Journal Article Date: 2008-03-12 |
Journal Detail:
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Title: Clinical and experimental pharmacology & physiology Volume: 35 ISSN: 1440-1681 ISO Abbreviation: Clin. Exp. Pharmacol. Physiol. Publication Date: 2008 Jul |
Date Detail:
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Created Date: 2008-05-23 Completed Date: 2008-10-20 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0425076 Medline TA: Clin Exp Pharmacol Physiol Country: Australia |
Other Details:
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Languages: eng Pagination: 841-5 Citation Subset: IM |
Affiliation:
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Department of Emergency and Critical Care Medicine, Nippon Medical School, Tokyo, Japan. s-hara@nms.ac.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Consciousness / drug effects*, physiology Gastrointestinal Motility / drug effects*, physiology Glycine / administration & dosage, analogs & derivatives* Guinea Pigs Hypotension / chemically induced, physiopathology, prevention & control* Infusions, Intravenous Intestinal Diseases / chemically induced, physiopathology, prevention & control* Lipopolysaccharides / toxicity* Male Sulfonamides / administration & dosage* |
| Chemical | |
Reg. No./Substance:
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0/Lipopolysaccharides; 0/Sulfonamides; 127373-66-4/ONO 5046; 56-40-6/Glycine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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