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In vivo studies of ischaemia - reperfusion injury in hypothermically-stored rabbit renal autografts

Lane, Nicholas James; (1996) In vivo studies of ischaemia - reperfusion injury in hypothermically-stored rabbit renal autografts. Doctoral thesis (Ph.D.), University College London (United Kingdom). Green open access

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Abstract

Ischaemia-reperfusion injury is a major cause of graft failure following renal transplantation. These studies were undertaken to elucidate the pathogenesis of ischaemia-reperfusion injury and the effects of specific therapeutic interventions, with the aim of extending the 'safe' preservation period of kidneys stored prior to transplantation. An in vivo renal autograft model was used throughout. Mitochondrial function was assessed non- invasively using surface fluorometry and near infrared spectroscopy of respiratory chain components NADH and cytochrome oxidase. Changes in renal haemoglobin oxygenation and concentration were measured using near infrared spectroscopy. Pathological markers were measured in assays of susceptibility to lipid peroxidation and enzyme immunoassays of plasma eicosanoid levels. Intra-renal perfusion was evaluated using barium sulphate angiography, micro-angiography and colloidal carbon vascular labelling. Morphological changes were evaluated using light and electron microscopy. Revascularization of stored kidneys led to the development of severe vascular congestion in the medulla and acute tubular necrosis in the cortex. Congestion was a consequence of ischaemic swelling of the medullary' thick ascending tubules, developing within 10 min of reperfusion and beginning to clear within 1 h. Respiratory chain dysfunction occurred rapidly upon reperfusion, persisted for at least 3 h and was independent of vascular congestion. Iron chelation attenuated susceptibility to lipid peroxidation and limited cortical necrosis but did not effect respiratory chain function, medullary congestion or long-term renal viability. Inhibition of inflammation using anti-inflammatory or antioxidant drugs also limited cortical necrosis but had no effect on medullary congestion or long-term viability. Medullary tubular dysfunction was shown to be responsive to but not prevented by substitution of impermeant solutes, as judged by changes in tissue oxygenation following infusions of the diuretic frusemide. It is concluded that renal ischaemia-reperfusion injury is a consequence of several concurrent pathological changes and that effective therapy must be targeted to several specific cell types

Type: Thesis (Doctoral)
Qualification: Ph.D.
Title: In vivo studies of ischaemia - reperfusion injury in hypothermically-stored rabbit renal autografts
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: (UMI)AAIU092479; Health and environmental sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10101831
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