Hamilton-Davies, Colin; (1998) The role of pre-operative endotoxin core antibody (EndoCAb) status in outcome following cardiac surgery and approaches to elevating EndoCAb. Doctoral thesis (Ph.D.), University College London (United Kingdom).

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Abstract

Multiple organ failure is thought to be the end-stage of a spectrum of complications related to activation of the body's inflammatory system by a series of triggers. It is also a major cause of death in intensive care units and can arise in patients following elective high-risk surgery. Endotoxin is one such trigger and evidence has demonstrated its presence in excess during the course of surgery involving cardiopulmonary bypass. This thesis examines previous endotoxin-related research into the field of sepsis and high-risk surgery and explores the hypothesis that the patient's own endogenous immunity to the core moiety of endotoxin may influence the post-operative outcome following cardiac surgery. Intra-operative monitoring consisted of both routine and non-routine methods of haemodynamic assessment and indicators of gut perfusion. In my initial observational study on patients undergoing first-time cardiac valve replacement and the follow-up collaborational study with Duke University Medical Centre patients were pre-operatively Parsonnet risk scored. It was found that in both studies pre-operative IgM endotoxin core antibody (EndoCAb) levels were predictive of the development of post-operative complications independent of the Parsonnet risk score. In the initial study where gastrointestinal tonometry was used as a monitor it was found that by combining the preoperative IgM EndoCAb levels with the end-surgery gastrointestinal intramucosal:arterial PCO2 gap the previously quoted poor specificity of the tonometer for detecting complications could be markedly improved. Also in the initial study where plasma markers of neutrophil and contact activation were measured it was demonstrated that certain markers indicated a greater degree of activation in the 25% of patients with the lowest pre-operative IgM EndoCAb levels. Peri-operative usage of blood products was also found to be higher in those patients with lower pre-operative EndoCAb levels. The remainder of this thesis concentrates on examining methods of elevating EndoCAb by means of active and passive immunisation and also studying the effect of various grades of exercise on the EndoCAb status of volunteers.

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