| Nitroglycerin prevents coagulopathies and foetal death associated with abnormal maternal inflammation in rats. | |
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MedLine Citation:
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PMID: 22274747 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Inflammation-associated foetal loss is often linked to maternal coagulopathies. Here, we characterised the role of maternal inflammation in the development of various systemic maternal coagulopathies and foetal death during mid-to-late gestation in rats. Since nitric oxide (NO) functions as an inhibitor of platelet aggregation and anti-oxidant, we also tested whether the NO mimetic nitroglycerin (glyceryl trinitrate, GTN) prevents inflammation-associated coagulopathies and foetal death. To induce chronic inflammation, pregnant Wistar rats were injected with low-doses of lipopolysaccharide (LPS; 10-40 μg/kg) on gestational days (GD) 13.5-16.5. To determine whether the effects of inflammation are mediated by tumour necrosis factor-α (TNF-α), the TNF-α inhibitor etanercept was injected on GD 13.5 and 15.5. Controls consisted of rats injected with saline. GTN was administered to LPS-treated rats via daily application of a transdermal patch on GD 12.5-16.5. Using thromboelastography (TEG), various coagulation parameters were assessed on GD 17.5; foetal viability was determined morphologically. Reference coagulation parameters were established based on TEG results obtained from control animals. LPS-treated rats exhibited distinct systemic coagulopathies: hypercoagulability, hypocoagulability, hyperfibrinolysis, and disseminated intravascular coagulation (DIC) stages I and III. A specific foetal death coagulation phenotype was observed, implicating TEG as a potential tool to identify inflammation-induced haemostatic alterations associated with pregnancy loss. Treatment with etanercept reduced the incidence of coagulopathy by 47%, while continuous delivery of GTN prevented foetal death and the inflammation-induced coagulopathies. These findings provide a rationale for investigating the use of GTN in the prevention of maternal coagulopathies and inflammation-mediated foetal death. |
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Authors:
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Tiziana Cotechini; Maha Othman; Charles H Graham |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2012-01-25 |
Journal Detail:
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Title: Thrombosis and haemostasis Volume: 107 ISSN: 0340-6245 ISO Abbreviation: Thromb. Haemost. Publication Date: 2012 May |
Date Detail:
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Created Date: 2012-05-02 Completed Date: 2012-08-27 Revised Date: 2012-10-31 |
Medline Journal Info:
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Nlm Unique ID: 7608063 Medline TA: Thromb Haemost Country: Germany |
Other Details:
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Languages: eng Pagination: 864-74 Citation Subset: IM |
Affiliation:
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Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Administration, Cutaneous Animals Blood Coagulation / drug effects* Blood Coagulation Disorders / blood, etiology, prevention & control* Female Fetal Death / blood, etiology, prevention & control* Gestational Age Immunoglobulin G / pharmacology Inflammation / blood, chemically induced, complications, drug therapy* Inflammation Mediators / metabolism Lipopolysaccharides Nitroglycerin / administration & dosage, pharmacology* Phenotype Pregnancy Rats Rats, Wistar Receptors, Tumor Necrosis Factor Thrombelastography Time Factors Transdermal Patch Tumor Necrosis Factor-alpha / antagonists & inhibitors, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Immunoglobulin G; 0/Inflammation Mediators; 0/Lipopolysaccharides; 0/Receptors, Tumor Necrosis Factor; 0/Tumor Necrosis Factor-alpha; 0/lipopolysaccharide, Escherichia coli 0111 B4; 185243-69-0/TNFR-Fc fusion protein; 55-63-0/Nitroglycerin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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