Out-of-theatre intubation frequently occurs in the absence of essential safety equipment, despite the existing guidelines. The associated adverse event rate is high.
Problem
Angiogenic imbalance during pregnancy is associated with immune activation, hypertension, increased T cell infiltration, and neurological insults.
Method of Study
On gestational day (GD) 12 timed-pregnant rats were infused with anti-angiogenic factors sFlt-1 and sEndoglin (4.7 and 7μg/kg) to create HELLP syndrome via mini-osmotic pumps for 8 days, with a subset of these rats having Orencia (2mg/kg) infused on GD13. On GD19, blood brain barrier (BBB) permeability was evaluated via Evan’s Blue infusion, blood was collected for T cell measurements, inflammatory cytokine secretion. Brain tissues were also collected to examine inflammatory cytokine infiltration.
Results
T cell attenuation with Orencia decreased circulating CD4+ and CD8+ T cells, circulating TNFα and IL-17, BBB permeability and significantly decreased biochemical evidence of HELLP compared to untreated HELLP rats.
Conclusions
These data support the hypothesis that T cells have a critical role in contributing to the pathophysiology that is seen in angiogenic imbalance during pregnancy.
Hypertension and inflammation during pregnancy are suggested to contribute to the development of post-partum depression and anxiety. Using a rat model of severe preeclampsia and Hemolysis Elevated Liver enzymes Low Platelet syndrome which displays both hypertension and inflammation during pregnancy we evaluated whether rats were prone to develop depression or anxiety in the post-partum period. On gestational day 12, mini-osmotic pumps infusing sFlt-1 and sEng were placed into rats, a subset of these rats were infused with 2mg/kg of Orencia (Abatacept) the following day to determine if immune suppression via T cell depletion prevented any changes in maternal depression and/or anxiety-like behavior. All rats including normal pregnant controls delivered between gestational days 21–22. Post-partum severe preeclamptic rats buried significantly more marbles compared to normal pregnant rats (p=0.002) and Orencia treated rats (p=0.05). Severe preeclamptic rats spent significantly more time in closed arms of the elevated plus maze compared to normal pregnant rats (p=0.009) and Orencia treated rats (p=0.05). Severe preeclamptic rats were hypertensive compared to normal pregnant (p=0.03) and Orencia treated rats (p=0.01). Finally, severe preeclamptic rats had increased blood brain barrier permeability compared to normal pregnant rats (p=0.03), which was reversed in Orencia treated rats (p=0.008). These results suggest that severe preeclampsia/Hemolysis Elevated Liver enzymes Low Platelet syndrome during pregnancy contributes to an increase in anxiety-like behavior, blood brain barrier permeability and hypertension in the post-partum. The current results suggest that T cell suppression during pregnancy can also help prevent chronic hypertension and increased anxiety in the post-partum period.
Introduction
Placental FasL is up-regulated in women with HELLP (hemolysis elevated liver enzyme and low platelet) syndrome and has been proposed to contribute to the liver damage seen in these patients.
Objective
This study aimed to determine if an experimental rodent model of HELLP also had dysregulation of Fas/FasL compared to normal pregnant (NP) rats. We also set out to determine if blockade of the endothelin system regulated Fas/FasL expression in HELLP rats.
Study Design
On gestational day (GD) 12, sEng (7ug/kg) and sFlt-1 (4.7ug/kg) infusion began via mini-osmotic pump into NP rats. On GD19 plasma and tissue were collected and FasL and Fas were measured via enzyme linked immunosorbent assay and gene expression via real-time PCR.
Results
HELLP rats had significantly more circulating and placental FasL compared to NP rats, whereas hepatic FasL was decreased and placental Fas was increased compared to NP rats. Administration of an endothelin A receptor antagonist (ETA) beginning on GD12 significantly decreased placental expression of Fas in HELLP rats. Liver mRNA transcript of Fas was significantly increased in HELLP rats compared to NP rats).
Conclusion
These data suggest that rats in this experimental model of HELLP syndrome have abnormal expression of the Fas/FasL system. Future studies will examine the sources of Fas/FasL dysregulation in this model and if blockade could reduce some of the inflammation and hypertension associated with HELLP syndrome.
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