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Title: In vivo monitoring of human intestinal ischaemia : an on-line rapid sampling microdialysis biosensor system
Author: Corcoles, Emma P.
ISNI:       0000 0004 2680 5712
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2009
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The primary aim of this thesis was to monitor in vivo intestinal ischemia using rapid sampling on-line microdialysis. A new variant of a clinical assay system was developed for use in gastrointestinal surgery. The assay could process on-line microdialysis samples for glucose and lactate concentrations at 30 seconds intervals in the concentration range of 25 μM to 30 mM. Intramural human bowel ischaemia was monitored intra-operatively in a clinical collaboration with Prof. Darzi and Prof. Hanna in St. Maryʼs Hospital, London using a microdialysis probe implantation technique devised by Mr. Samer Deeba. Dialysate levels stabilised within 10-15 minutes following implantation of the CMA 62 microdialysis probe. Clipping of arteries feeding the gastrointestinal tissue to be resected, did not lead to an immediate change in dialysate levels, but a fall in glucose and rise in lactate delayed by 17 ± 2 minutes, n=9. This suggests an additional pool of glucose availability in the bowel, and indicates a possible therapeutic window during bowel surgery. Parallel experimental work was carried out in swine model in the surgical labs of the healthcare company Tyco (Covidien) in Paris. Rapid sampling microdialysis was used to examine the effect of total ischaemia on an anastomosis site. The anastomotic site was devascularised by clamping the mesentery of both sides. Here the tissue reacted to ischaemia immediately, 5 minutes following clamping of feeding artery, compared with a healthy human bowel, suggesting that the additional glucose pool was unavailable in this situation. Physiological variable effects were studied to investigate further any difference with respect to the human in pig bowel physiology, which were not found. The no-net-flux method of in vivo recovery was used to determine the extracellular levels of glucose (0.47 ± 0.05 mM) in the intramural pig bowel. These were substantially lower than blood glucose values, representing a 10% of plasma levels and suggest a difference with human bowel. Finally, 7 patients were monitored after abdominal aortic aneurism repair surgery, for up to 2 days in the intensive care unit, to detect the possible on-set of ischaemia as a complication of inferior mesenteric artery occlusion. Basal microdialysis levels at 3.98 ± 0.75 mM for glucose and 1.38 ± 0.20 mM for lactate agreed well with those measured acutely during surgery, and were not sensitive to changes in plasma values. The lactate/glucose ratio between 1-2 days post-implantation was typically between 0.5-1.0 again similar to the ratio found intra-operatively. This validates the use of microdialysis intra-operatively and confirms the importance of this ratio. An in vivo calibration was performed in one patient with the variable flow rate method providing extracellular levels for glucose (5.8 ± 0.4 mM) and lactate (3.3 ± 0.2 mM) in intramural human bowel. These agree well with measured blood glucose values. Although major ischaemic failure was not seen in these patients, transient ischaemic events lasting 40 minutes and characterised by a lactate/glucose ratio increase to 2 were noticed. Finally, a quasi-periodic oscillatory pattern with inverse changes in glucose and lactate was observed during these patientsʼ monitoring. This was ascribed to gut peristalsis.
Supervisor: Boutelle, Martyn Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral