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Studies in reperfusion injury and its role in the immediate graft function following liver transplantation

The aims of this thesis were: 1. To investigate the changes in reactive oxygen intermediates (ROIs) and that of neutrophil activation during liver transplantation with emphasis on assessing their role on reperfusion injury and outcome of graft function. 2. To ascertain the place of indocyanine green clearance (ICG) test in early prediction and assessment of graft function after liver transplantation. 3. To evaluate the role played by two major vasoactive mediators in the development of the haemodynamic changes which often occur following graft reperfusion in liver transplantation. These are: the endothelins; the most potent biological smooth muscle vasoconstrictors, and guanosine 3', 5'-cyclic mono-phosphate (cGMP); the secondary messenger of nitric oxide (NO) and atrial natriuretic peptide (ANP) which mediates vasorelaxation. This thesis has provided evidence of increasing ROIs activity following reperfusion of liver grafts and the magnitude of changes correlated with the severity of graft dysfunction. It also demonstrated that a significant degree of neutrophil activation occurs following graft reperfusion with evidence of endothelial cell damage as a result of such activity. This thesis has shown that an ICG clearance <200ml/min measured within 24 hrs following liver transplantation predicted graft dysfunction due to reperfusion injury with high specificity and sensitivity. Finally this thesis has demonstrated that the haemodynamic changes following reperfusion of liver graft during transplantation involve predominantly the pulmonary vasculature. It also demonstrates that these changes correlated significantly with a reduction in the levels of cGMP, which suggests a causal relationship. The endothelins levels in blood were raised before transplantation and remained so post-reperfusion, with no evidence of a role to play in the haemodynamic changes during transplantation.

Identiferoai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:642289
Date January 1998
CreatorsBzeizi, Khalid I.
PublisherUniversity of Edinburgh
Source SetsEthos UK
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Sourcehttp://hdl.handle.net/1842/21667

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