Endoscopic Measurements of Mitochondrial Oxygen Tension: a pilot study

Adequate oxygen supply to the tissues is a required condition for human life,
moreover for life of all mammalians. Adequate and reliable measurements of
tissue oxygenation are important for diagnosis and treatment decisions in a
broad spectrum of diseases. Many techniques have been developed for oxygen
measurements in vivo but the ultimate goal is to measure oxygen at the lowest
level, at the mitochondria. Mik et al. introduced the protoporphyrin IX-triplet
state lifetime technique (PpIX-TSLT) for measuring PO2 in mitochondria
(mitoPO2). The technique resulted in the development of the COMET monitor, a
clinical monitor for assessment of Cellular Oxygen METabolism, allows cutaneous
mitoPO2 measurements to be made in humans5. This non-invasive technique is not
yet tested in the stomach and small intestine during upper endoscopy. If it is
possible to measure mitoPO2 in the gastrointestinal tract, many purposes are
supposable. For example, mitoPO2 measurements can be used in the work-up of
chronic gastrointestinal ischemia (CGI). CGI is the result of insufficient
blood supply to the gastrointestinal tract. Patients with chronic
gastrointestinal ischemia (CGI) suffer from severe postprandial abdominal pain
and weight loss, usually caused by atherosclerotic stenosis of the supplying
gastrointestinal arteries. The diagnosis of CGI remains challenging as chronic
abdominal pain due to other causes is common and stenosis of the mesenteric
arteries are often asymptomatic due to extensive collateral circulation. The
standard diagnostic work up includes assessment of clinical symptoms,
radiological imaging and a functional test as visible light spectroscopy (VLS)
or tonometry resulting in an expired-based consensus diagnosis. Current
diagnostic work-up is extensive with various investigations in the absence of
just one specific test to diagnose CGI. Hence, a reliable, non-invasive test is
needed to assess the oxygenation of the gastrointestinal tract.

To determine the feasibility of the MitoPO2 measurements during upper
endoscopy.

Inclusion
Healthy volunteers with no gastrointestinal complaints and unremarkable medical
history will be asked to participate in our study through information folders
in the Erasmus MC, Rotterdam. This folder will provide information about the
study and the study procedure, and also how to contact the research
investigator. If people are interested, they can contact the coordinating
investigator for a consult to obtain further information. They will receive the
patient information folder. If a healthy volunteer decides to participate in
the study, he or she will sign the Informed Consent Form and the abdominal
duplex ultrasound to determine patent gastrointestinal arteries and the upper
endoscopy will be scheduled.

Intervention
The healthy volunteers will drink 5-aminolevulinic acid (ALA, Gliolan 30 mg/ml)
4 hours before the upper endoscopy. The dose of Gliolan will be 20 mg/kg
weight. Four hours after the administration of Gliolan the upper endoscopy
will be performed.
Healthy volunteers can choose if they want sedation or not during the
endoscopy. Sedation will be 2.5-5 mg midazolam combined with 0.05 mg fentanyl
intravenously prior to the endoscopy. The MitoPO2 measurements will be
performed with the COMET measurement system during upper endoscopy using a
sterile single use fiberoptic-catheter (MUCS000001, LightGuideOptics,
Germany),that can be passed through the accessory channel of the endoscope.
Measurements of the MitoPO2 will be performed at three sites in the stomach and
duodenum: antrum of the stomach, descending duodenum and duodenal bulb. Three
repeated readings will be taken at different areas of each location. The
average of the three readings per location will be regarded as the actual
measurement of that specific location. After three MitoPO2 measurements at a
location, also three VLS measurements will be performed at that specific
location. A fiberoptic catheter-based oximeter (T-Stat 303 Microvascular
Oximeter, Spectros, Portola Valley, California, USA) will be passed through the
accessory channel of the endoscope. To prevent luminal spasms butylscopalamin
20mg is admitted intravenously before the start of VLS measurements.

Afterwards, healthy volunteers with sedation will be brought to the endoscopy
recovery room to sleep off. If no sedation is used, healthy volunteers are
required to go immediately after the endoscopy. It is important to notice that
they should avoid exposure to strong light sources (eg. direct sunlight or
brightly focused indoor light) of eyes and skin for 24 hours after
administration of Gliolan. The total duration of the upper endoscopy will be
15-20 minutes.

Follow-up
There is no follow-up of the healthy volunteers in this study. Obviously, if
during upper endoscopy findings are detected, the healthy volunteer will be
referred to our outpatient clinic for further analysis and treatment.

- risk of upper endoscopy without invasive intervention is very low, especially
when no sedation is used
- Visible Light Spectroscopy measurements are safe and non-invasive
- mitochondrial oxygen tension measurements are safe and non-invasive
- intake of Gliolan (ALA) causes photosensitivity, but when the participant
avoids exposure to strong light sources, there is no risk