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Title: The effects of S-nitrosoglutathione on vascular stiffness and platelet function in early-onset pre-eclampsia
Author: Everett , Thomas Richard
ISNI:       0000 0004 5372 6921
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2015
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Pre-eclampsia is a lead ing cause of maternal and fetal mortality and morbidity. Early-onset pre-eclampsia occurring before 32 weeks gestation affects ~1% of pregnancies. At these gestations conservative management focussing on control of hypertension and seizure prevention, to gain fetal maturity is key. Impaired nitric oxide bioavailability, is thought to play a major role in the maternal manifestations of pre-eclampsia such as hypertension and likewise platelet activation, proteinuria and oedema. There is no current treatment that targets the underlying pathophysiology. Uterine artery Doppler and arterial stiffness were assessed in ninety-nine women, at high a priori risk of pre-eclampsia. The study showed a positive correlation between increased uterine artery impedance and both pulse wave reflection (AI)() and aortic pulse wave velocity (aPWV). Alx was negatively correlated with neonatal birth weight. Infusion studies of S-nitrosoglutathione (GSNO) and labetalol, the standard antihypertensive used in pre-eclampsia, were performed in 12 healthy nonpregnant volunteers to assess the effects on Alx and aPWV and cardiac output. The study showed that GSNO and labetalol have similar effect on blood pressure, however GSI\lO, but not labetalol, reduces Alx. The primary outcome of the GSNO infusion study in preeclampsia was to establish the dose of GSNO at which there was optimal reduction in Alx, without causing a clinically significant fall in blood pressure. Secondary outcomes included the effect on platelet function, soluble biomarkers and proteinuria in the mother and Doppler parameters in both the mother and fetus. Six women underwent infusion and an infusion rate of 1O-30mcg/min GSNO was established as an optimal dose. GSNO significantly reduced platelet activation and trend towards reduction in proteinuria and soluble endoglin was seen. The effects of GSNO in women with preeclampsia and make GSNO a promising candidate for further investigation for the treatment of pre-eclampsia, either as a sole agent or adjunct to current treatments.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available