Patients with portal hypertension who have bled from oesophageal varices have a mortality of approximately 30&37 . It is a therapeutic paradox that life-saving resuscitation following haemorrhagic shock may be detrimental by causing variceal rebleeding or continued haemorrhage and by inducing gastric erosions. This thesis addresses the hypotheses: i) secondary bleeding from varices in portal hypertension (PHT) is precipitated by blood volume restitution resulting from increased portal pressure, an increase which can be prevented by the somatostatin analogue, SMS 201-995 (Octreotide); ii) erosive gastritis found in patients with varices results from increased susceptibility to mucosal injury, is exacerbated by reperfusion, and is mediated by oxygen-derived free radicals. The three principal approaches employed were initially to establish prehepatic portal hypertension in a rat model by graded portal vein ligation (PVL). Acute PHT (3 days post-PVL) was characterised by high portal pressure and little portasystemic shunting, while chronic PHT (14 days post-PVL) was characterised by lower portal pressure and increased shunting. In anaesthetised hypovolaemic animals, arterial pressure was reduced below 35mmHg for 30 minutes. Following reperfusion, portal pressure increased by up to 34&37 above baseline values. In acute PHT, this was mediated by increased portal venous inflow, whereas in chronic PHT, outflow resistance increased. The rise in portal pressure was prevented by SMS 201-995 (dose-related). Secondly, studies of the gastric mucosa in PHT demonstrated that; it was not more susceptible to injury; injury was dependent on gastric luminal acidity; a gradient of injury existed, and there was no correlation between injury and portal pressure or shunting.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:385609 |
| Date | January 1993 |
| Creators | Donald, James |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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