Nitroglycerin prevents coagulopathies and foetal death associated with abnormal maternal inflammation in rats.

Abstract

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
• Journal: Thrombosis and haemostasis (Thromb Haemost) Vol. 107 Issue 5 Pg. 864-74 (May 2012) ISSN: 2567-689X [Electronic] Germany
• PMID: 22274747 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Immunoglobulin G
• Inflammation Mediators
• Lipopolysaccharides
• Receptors, Tumor Necrosis Factor
• Tumor Necrosis Factor-alpha
• lipopolysaccharide, Escherichia coli O111 B4
• Nitroglycerin
• Etanercept

Topics

• Administration, Cutaneous
• Animals
• Blood Coagulation (drug effects)
• Blood Coagulation Disorders (blood, etiology, prevention & control)
• Etanercept
• 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)