Vipond, Mark Neil; (1992) Peritoneal fibrinolysis and intra-abdominal adhesions. Masters thesis (M.S), UCL (University College London).

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Abstract

Intra-abdominal adhesions are the commonest cause of small bowel obstruction in developed countries. Following peritoneal injury a fibrin-rich inflammatory exudate is released into the peritoneal cavity producing delicate fibrinous adhesions which are either lysed or become organised into permanent fibrous adhesions. Studies were undertaken to determine the relationship between peritoneal fibrinolysis and intra-abdominal adhesion formation. A fibrin plate method for quantifying functional fibrinolytic activity (measured as plasminogen activating activity: PAA) of the peritoneum was established and validated. Employing this assay fibrinolytic activity was identified in both animal and human peritoneum. Inflammation was shown to significantly reduce fibrinolytic activity in human parietal and visceral peritoneum. The timing of reduction of peritoneal fibrinolytic activity was investigated after ischaemic, bacterial and chemical peritonitis in rats. All three injuries resulted in adhesions and a similar profile of peritoneal fibrinolytic activity: an initial significant reduction of PAA lasting 24 hours followed by a rebound peak and return to basal levels at two weeks. Using antibody inhibition techniques tissue plasminogen activator (tPA), rather than urokinase, was shown to be the principal plasminogen activator in human peritoneum. In inflamed human peritoneum levels of tPA were unaltered but the fast acting plasminogen activator inhibitor-one (PAI-1), not present in normal peritoneum, was elaborated and associated with loss of functional fibrinolytic activity. The peritoneal exudate after elective surgery was found to have no fibrinolytic activity but high levels of PAI-1. These results contrasted with the findings in normal peritoneum and bile. Recombinant tPA combined with an inert slow-release gel was tested in an animal model of ischaemic adhesion formation. Gel alone reduced adhesion formation and the addition of rtPA significantly increased this effect. These studies indicate that peritoneal insults are accompanied by reduction in peritoneal fibrinolysis and provide a unifying pathophysiological mechanism for adhesion formation. Local delivery of the fibrin-specific agent tPA is able to reduce the formation of adhesions and this may prove to be a valuable adjunct in clinical practice.

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