The primary aims of the project were: i) to develop assays capable of detecting changes in endogenous fibrinolytic activity for use in animal models. ii) to determine whether changes in endogenous fibrinolytic activity could be achieved following administration of a range of pharmacologically active agents. iii) to investigate the effect of such changes in endogenous fibrinolytic activity on thrombus formation and lysis in a suitable animal model <i>in vivo</i>. 1. Methods established for estimation of fibrinolytic activity in the plasma of rats and rabbit comprised chromogenic activity assays measuring tPA and PAI activity and the euglobulin clot lysis time assay as an index of fibrinolytic capacity. Changes in either plasma tPA or plasma PAI levels correlated well with changes in fibrinolytic activity as measured by the euglobulin clot lysis time assay; this comparison has previously not been carried out in animal studies. 2. A range of animal tests were investigated in an attempt to identify a paradigm of disease compromised fibrinolytic activity. Again, a systematic approach of this type had not previously been carried out in animals. The most significant alteration in plasma fibrinolytic activity was seen in the arthritic rabbit where levels of PAI and the acute phase reactant fibrinogen were significantly elevated. These data provide new evidence demonstrating PAI acting as an acute phase reactant in an animal model of inflammation. 3. Compounds were identified that either possessed pro-fibrinolytic actions (by elevating endogenous tPA activity or inhibiting endogenous PAI activity) or were shown to inhibit fibrinolytic activity (increased plasma PAI activity).
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:358267 |
| Date | January 1993 |
| Creators | Jamieson, Alec |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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