In vivo monitoring of human intestinal ischaemia: An on-line rapid sampling microdialysis biosensor system
Author(s)
Corcoles, Emma P.
Type
Thesis
Abstract
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.
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.
Date Issued
2009-03
Date Awarded
2009-08
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Boutelle, Martyn
Creator
Corcoles, Emma P.
Publisher Department
Bioengineering
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)