Document Detail


Nitroglycerin prevents coagulopathies and foetal death associated with abnormal maternal inflammation in rats.
MedLine Citation:
PMID:  22274747     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Tiziana Cotechini; Maha Othman; Charles H Graham
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-01-25
Journal Detail:
Title:  Thrombosis and haemostasis     Volume:  107     ISSN:  0340-6245     ISO Abbreviation:  Thromb. Haemost.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-05-02     Completed Date:  2012-08-27     Revised Date:  2012-10-31    
Medline Journal Info:
Nlm Unique ID:  7608063     Medline TA:  Thromb Haemost     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  864-74     Citation Subset:  IM    
Affiliation:
Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
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MeSH Terms
Descriptor/Qualifier:
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:
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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