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Title: Effects of intestinal ischaemia and reperfusion on the gut and liver
Author: Williams, Susan Beris
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 2004
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Intestinal ischaemia-reperfusion (IIR) injury is a life-threatening condition affecting adults and children. Common causes include acute mesenteric ischaemia, volvulus, intussusception, necrotizing enterocolitis, sepsis and trauma. IIR triggers a cascade of inflammatory mediators, increases intestinal permeability and results in local and remote organ damage. The liver is especially prone to IIR-associated dysfunction. Adults and children respond to IIR injury in subtly different ways. This thesis reports an investigation of a rat model of IIR (90 minutes intestinal ischaemia then 60 minutes reperfusion under general anaesthetic) and describes IIR-related changes in the liver, blood composition and gut. Hepatic tissue metabolites were measured after IIR in suckling and adult rats. In both age groups ATP fell and inorganic phosphate (Pi) and alanine rose after IIR. Adult rats had higher levels of total hepatic glutathione, and hepatic glutamine fell after IIR. Hepatic lactate and succinate rose in suckling rats after IIR. Blood composition changed after IIR in adult rats - Pi rose, haematocrit rose, pH fell, and blood oxygen content rose. Systemic, but not portal, arterio-venous difference in oxygen content rose. Hepatic inflow fell with prolonged intestinal reperfusion, which was partially abrogated by whole-body hypothermia (32 0.5 C). Hypothermia also reduced IIR-related changes in blood composition and hepatic tissue metabolites, abolishing the relationship of the latter with final total hepatic inflow. IIR was associated with rises in plasma tumour necrosis factor-alpha, interleukins 6 and 10, and endotoxin. These rises were significantly reduced by hypothermia. Correlation of intestinal arterial inflow and intestinal tissue oxygenation index during IIR demonstrated a complex relationship. In conclusion, IIR perturbs hepatic metabolism, blood composition, hepatic inflow, and plasma cytokine and endotoxin levels. Some of these effects are abrogated by hypothermia. It is possible to follow intestinal tissue oxygenation during IIR with near infra-red spectroscopy. These latter observations may have clinical significance.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available