PMID- 22274747
OWN - NLM
STAT- MEDLINE
DCOM- 20120827
LR  - 20160627
IS  - 2567-689X (Electronic)
IS  - 0340-6245 (Linking)
VI  - 107
IP  - 5
DP  - 2012 May
TI  - Nitroglycerin prevents coagulopathies and foetal death associated with abnormal 
      maternal inflammation in rats.
PG  - 864-74
LID - 10.1160/TH11-10-0730 [doi]
AB  - 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 mug/kg) on gestational days (GD) 
      13.5-16.5. To determine whether the effects of inflammation are mediated by 
      tumour necrosis factor-alpha (TNF-alpha), the TNF-alpha 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.
FAU - Cotechini, Tiziana
AU  - Cotechini T
AD  - Department of Biomedical and Molecular Sciences, Queen's University, Kingston, 
      ON, Canada.
FAU - Othman, Maha
AU  - Othman M
FAU - Graham, Charles H
AU  - Graham CH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120125
PL  - Germany
TA  - Thromb Haemost
JT  - Thrombosis and haemostasis
JID - 7608063
RN  - 0 (Immunoglobulin G)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (lipopolysaccharide, Escherichia coli O111 B4)
RN  - G59M7S0WS3 (Nitroglycerin)
RN  - OP401G7OJC (Etanercept)
SB  - IM
MH  - Administration, Cutaneous
MH  - Animals
MH  - Blood Coagulation/*drug effects
MH  - Blood Coagulation Disorders/blood/etiology/*prevention & control
MH  - Etanercept
MH  - Female
MH  - Fetal Death/blood/etiology/*prevention & control
MH  - Gestational Age
MH  - Immunoglobulin G/pharmacology
MH  - Inflammation/blood/chemically induced/complications/*drug therapy
MH  - Inflammation Mediators/metabolism
MH  - Lipopolysaccharides
MH  - Nitroglycerin/administration & dosage/*pharmacology
MH  - Phenotype
MH  - Pregnancy
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Tumor Necrosis Factor
MH  - Thrombelastography
MH  - Time Factors
MH  - Transdermal Patch
MH  - Tumor Necrosis Factor-alpha/antagonists & inhibitors/metabolism
EDAT- 2012/01/26 06:00
MHDA- 2012/08/28 06:00
CRDT- 2012/01/26 06:00
PHST- 2011/10/21 00:00 [received]
PHST- 2011/12/22 00:00 [accepted]
PHST- 2012/01/26 06:00 [entrez]
PHST- 2012/01/26 06:00 [pubmed]
PHST- 2012/08/28 06:00 [medline]
AID - 11-10-0730 [pii]
AID - 10.1160/TH11-10-0730 [doi]
PST - ppublish
SO  - Thromb Haemost. 2012 May;107(5):864-74. doi: 10.1160/TH11-10-0730. Epub 2012 Jan 
      25.