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Title: Inhibition of neutrophil activation : effects in reperfusion injury and cardiopulmonary bypass
Author: Wanikiat, Payong
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2000
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The aims of this thesis were: 1) to establish the role of nitric oxide (NO) and cyclic GMP in neutrophil chemotaxis and superoxide anion generation (SAG), 2) to investigate the effects of a novel NO donor GEA 3162, the A2A receptor agonist 2-HE-NECA, and the PGI2 analogue cicaprost on neutrophil accumulation and myocardial injury in vivo, in a rat model of MI-R, and 3) to identify the role of neutrophil activation in the formation of stable platelet aggregates and whether heparin, which is used systematically to anticoagulate for CPB, contributed to platelet dysfunction during CPB by interfering with neutrophil-platelet interactions. Effects of heparin in vitro, on neutrophil SAG and myeloperoxidase release were also determined. The mechanisms responsible for chemotaxis and neutrophil activation are not fully understood. Selective inhibitors of the NO and cyclic GMP pathways have been used to elucidate their roles in the activation and inhibition of human neutrophils. In addition, the ability of NO donors to inhibit neutrophil chemotaxis was compared with their ability to increase neutrophil nitrate/nitrate and cyclic GMP levels. The results confirm that neutrophil activation results from the stimulation of several signal transduction systems. It appears that chemotaxis can occur via a NO-dependent as well as NO-independent pathway. Similar pathways appear to operate in SAG. The results also suggested that the small concentrations of NO and cyclic GMP induced by fMLP activated neutrophils while large concentrations of NO and cyclic GMP are inhibitory. The effects of GEA 3162, 2-HE-NECA, and cicaprost on neutrophil accumulation and myocardial injury in a rat model of MI-R were investigated. Myocardial ischaemia was induced by occlusion of the left main coronary artery (45 min) and then reperfused (120 min). Drugs or saline vehicle were infused intravenously for 130 min beginning 10 min before reperfusion. Neutrophil accumulation in the area at risk and normal area was assessed by myeloperoxidase assay.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available