Kubba, Tamara;
(2022)
An investigation of the maternal vascular response to ischaemic pre-conditioning in pre-eclampsia.
Doctoral thesis (Ph.D), UCL (University College London).
Preview |
Text
Kubba1_ Corrected Thesis.pdf - Other Download (1MB) | Preview |
Abstract
Pre-eclampsia is a syndrome of pregnancy, classically defined by the gestational-onset of hypertension and proteinuria. Pre-eclampsia complicates 4% of first-time pregnancies and contributes to maternal and neonatal morbidity and mortality globally. Women with pre-eclampsia have reduced utero-placental blood flow, compromising placental and fetal growth. This triggers maternal endothelial dysfunction and variable organ dysfunction. Outside pregnancy, repeated episodes of transient organ ischaemia, (ischaemic pre-conditioning: IPC) has improved endothelial function and blood flow to remote organs. IPC has not previously been tested in pregnancy. The main hypothesis is that local IPC improves endothelial function in women with established pre-eclampsia, as measured by brachial artery flow-mediated dilatation (FMD). To investigate how IPC may improve endothelial function, levels of vasoactive factors were assayed. I first investigated healthy non-pregnant women of childbearing age (n=24) to determine the time-interval following IPC that gave the greatest improvement in FMD. Having identified a 24-hour study interval, I carried out FMD before and after IPC in healthy normotensive pregnant women (n=42), women at risk of pre-eclampsia (n=20), and women with established pre-eclampsia (n=10). The results demonstrate that IPC significantly improves endothelial function in women with pre-eclampsia and at risk of pre-eclampsia (3.5% to 5.8% and 7.6% to 8.9% respectively, vs 10.3% to 10.5% in healthy women). IPC also shortened the time to reach peak FMD in healthy pregnant women. As expected, women with pre-eclampsia had higher sFlt-1 and lower PlGF levels, and higher sFlt1:PlGF ratios. Following IPC, there were no changes to these levels, nor consistent changes to levels of SDF-1, DPP-4 or VEGF. In conclusion, my results suggest that local IPC improves endothelial function in women with pre-eclampsia and at risk of pre-eclampsia. The relative simplicity and cost-effectiveness of IPC, make it an attractive intervention worthy of further investigation as a prophylaxis or treatment of pre-eclampsia.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | An investigation of the maternal vascular response to ischaemic pre-conditioning in pre-eclampsia |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2022. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10158780 |
Archive Staff Only
 |
View Item |
