eprintid: 10121563
rev_number: 8
eprint_status: archive
userid: 695
dir: disk0/10/12/15/63
datestamp: 2021-02-11 14:10:05
lastmod: 2021-02-11 14:10:05
status_changed: 2021-02-11 14:10:05
type: thesis
metadata_visibility: show
creators_name: Fernando, Bimbi Shiran
title: Oxidant stress and the hyperdynamic circulation in portal hypertension
ispublished: unpub
keywords: Biological sciences; Health and environmental sciences
note: Thesis digitised by ProQuest.
abstract: The partial portal vein ligation rat model of portal hypertension is associated with the development of a hyperdynamic circulation characterised by an increased cardiac index and a reduced systemic vascular resistance. Recent studies have shown that tumour necrosis factor-α is involved in the development of the hyperdynamic response. Studies on tumour necrosis factor-α in vitro have shown that the signal transduction pathways involve activation of the transcription factor NF-κB by reactive oxygen species and that this can be inhibited by antioxidants. It is not known however, whether involvement of these pathways can be demonstrated in vivo in this model, and whether treatment with antioxidants can inhibit these signalling pathways and thus the development of the hyperdynamic circulation. This thesis concentrated on the signal transduction pathways and the possible role of oxidant stress in the generation of the hyperdynamic circulation in the partial portal vein ligated rat model compared with sham controls. Firstly, a group of compounds known as the F2-isoprostanes were studied as markers of lipid peroxidation. Secondly, activation of the transcription factor NF-κB was measured in whole liver from different study groups. Levels of plasma TNF-α levels were then measured, as were plasma levels of nitrite and nitrate. Finally, haemodynamic studies were performed in different groups to evaluate the pharmacodynamic effects of different reagents including N-acetylcysteine, pyrrolidine dithiocarbamate and BB-1101. Partial portal vein ligation is associated with increased lipid peroxidation, activation of hepatic NF-κB and increased nitric oxide synthesis. Furthermore, the hyperdynamic circulation can be inhibited by the chronic administration of N-acetylcysteine, pyrrolidine dithiocarbamate and BB-1101 to PPVL rats. The precise mechanism of action of these reagents remains unclear and further work needs to be performed to answer these questions.
date: 1999
oa_status: green
full_text_type: other
thesis_class: doctoral_open
thesis_award: M.D
language: eng
primo: open
primo_central: open_green
verified: verified_manual
full_text_status: public
pages: 131
institution: University of London, Royal Free Hospital School of Medicine
thesis_type: Doctoral
citation:        Fernando, Bimbi Shiran;      (1999)    Oxidant stress and the hyperdynamic circulation in portal hypertension.                   Doctoral thesis  (M.D), University of London, Royal Free Hospital School of Medicine.     Green open access   
 
document_url: https://discovery-pp.ucl.ac.uk/id/eprint/10121563/1/Oxidant_stress_and_the_hyperdy.pdf